Distribution of Parenting styles and their hybrids
\r\n\tThis book intends to provide readers with a comprehensive overview of the basic mechanisms of siRNA, progress in the development of safer delivery vehicles, current developments in siRNA-based therapeutics and state-of-the-art technology and platforms with evidence-based clinical applications of siRNA.
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Dr. Nawaz did his PhD from University of Sao Paulo, Ribeirao Preto Medical School (Brazil), where he worked on transcriptomic and microRNAs (miRNAs) profiling in the malignant progression of brain tumors (gliomas) with an aim to identify potential therapeutic targets and non-invasive biomarkers. During his PhD, Dr. Nawaz was granted with fellowship from FAPESP (the highest ranked funding body in Brazil), and was also awarded with Science without borders mobility award from Brazilian higher education agency (CAPES) to join the University of Gothenburg for one year PhD exchange, where he worked on mechanisms of packaging therapeutic RNAs into exosomes, which are now used as RNA delivery vehicles. Later, he continued his Postdoc at the University of Gothenburg. He has also served community services, and is the founder of Biochemists Association QUA Islamabad (BAQI), and is junior member of international society for extracellular vesicles (ISEV). Dr. Nawaz has won several awards, both from Brazil, and Sweden, has participated in several international conferences, and has published research papers in reputed peer reviewed international journals. He also serves as reviewer for different journals (https://publons.com/author/1268786/). \nCurrently, Dr. Nawaz is working on stem cell-derived exosomes in tissue repair and regenerative medicine and using exosomes as RNA delivery vehicles and Drug Delivery (siRNA, RNAi, and mRNA based therapy).",institutionString:"University of Gothenburg",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Sao Paulo",institutionURL:null,country:{name:"Brazil"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"6",title:"Biochemistry, Genetics and Molecular Biology",slug:"biochemistry-genetics-and-molecular-biology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"286446",firstName:"Sara",lastName:"Bacvarova",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/286446/images/8491_n.jpg",email:"sara.b@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"45773",title:"Cultural Variations in Parenting Styles in the Majority World Evidences from Nigeria and Cameroon",doi:"10.5772/57003",slug:"cultural-variations-in-parenting-styles-in-the-majority-world-evidences-from-nigeria-and-cameroon",body:'From anthropological perspective culture may be defined as a whole complex of traditional behaviour which includes knowledge, belief, art, law, morals, religion and customs, and any other capabilities, and habits, that have been acquired and developed by the human race, as members of societies, and which is successively learned by each generation. In addition culture also consists of learned ways of acting, feeling and thinking, [1, 2]. The implication from this definition is that culture could be learned, acquired, experienced, and transmitted from one generation to another generation, or can be transferred from one place to another through acculturation.
From psychological perspective culture was conceptualised as a dynamic and socially interactive process and as comprising of two components [3]. One component deals with the creation of shared activity which is reflected in the cultural practices of members of the society. The second component deals with the creation of shared meaning which leads to cultural interpretations collectively given to behavioural patterns in the society. The cultural practices are regarded as the material side of culture while the shared meaning represents the symbolic side of culture and the interpretation and evaluation of the world. This perspective signifies the fact that culture is both inside and outside the individual [3].
From cross cultural perspective, two types of cultures have been identified and differentiated into individualistic and collectivistic cultures [4]. From this perspective it is believed that culture shapes people’s values and beliefs, and that specific attitudes and values differ between the individualistic and collectivistic societies [4].
Individualistic cultures tend to give priority to independence and the pursuit of individual achievement, whereas collectivistic cultures tend to place more emphasis on the individual’s contribution to the well-being of the family and the community [5]. The implication here is that there are cultural differences between individualistic and collectivistic societies, and these differences are variations in values that are of particular importance to each society and differential emphases placed upon particular practices in the society [3, 6]. The cultural values of a society thus shape people’s values in that society and consequently their interactions with their children and their parenting styles. This inference is what informed the deduction that in collectivistic countries parents tend to promote values such as helpfulness, conformity, and interdependence within the family [5].
The promotion of different values in different cultures would affect child outcomes in such cultures because each culture would have different goals and expectations of their citizens and children in such cultures would be socialized under different conditions. As such an effective parenting style in one culture may not be as effective as in other cultures. In a study carried out on cultural differences in parenting styles the researchers found cultural differences in effective parenting styles practiced by White American and Asian American families [7]. They found that White American families practiced authoritative parenting which involves support in form of (hugging and praising their children), and control in form of (setting clear expectations and moderate limits). These parental behaviours are also taken as parental warmth and acceptance. In the case of the Asian American families, who are made up of Chinese and Fillipino Americans, it was found that they are stricter in their parenting strategy and exhibit high control over their children and they lack warmth [7]. The researchers found that these Asian American families practice this parenting approach because they believe that control is necessary to parenting and strictness is an attempt to protect their children and not to inhibit them. They found that the Chinese Americans in particular value respect for authority, devotion to parents, emotional restraint (which is developed as a strategy for saving face later in life), and education. They also found that Chinese parents who train their children are very involved with their children’s lives and they must have been using these parenting strategies, ( e.g. authoritarian parenting strategy + involvement which indicates love), including (physical discipline -which they found difficult to practice in the U.S.), to achieve their goals of parenting which include developing these values in the children. They also found that the Fillipino Americans are interdependent and they depend on each other for support because they value reciprocal relationships. They also value affection and closeness and protection for their children especially their daughters. These values must have also guided their parenting strategies. In addition, it was also reported that first- generation Chinese youth from authoritarian homes do just as well in school as those from authoritative homes indicating that although authoritative parenting may benefit some ethnic groups it is not necessarily more beneficial than authoritarian parenting [7].
Families as social groups are influenced by the context around them and family relationships and parent-child interactions are each influenced by cultural context [4]. Depending on the culture therefore there are differences in child rearing practices. It has also been suggested that if parenting behaviour is consistent with cultural values then children in that culture will accept it [8], and if certain goals or expectations or attributes are preferred more in one culture compared to another then parents will likely place more emphasis on those particular attributes that are preferred in their culture for their children to acquire [9]. The implication here is that the culture in which one lives will likely impact on the particular type of parenting style that one uses or practices.
Baumrind (1971) categorized parenting strategies into three types of parenting style namely authoritarian, authoritative, and permissive parenting styles. She described authoritarian parenting as restrictive and punitive, placing firm limit and control on children with little or no verbal exchange, and is said to be associated with social incompetence and poor communication skills [11]. Authoritative parents put some limits and controls on their children’s actions, but they allow verbal dialogue which promotes parental responsiveness, encourages independence, social and cognitive competence, self reliance and social responsibility in the children. In permissive parenting few or no rules and little or no controls are exerted over the children. The children under this parenting style are given complete freedom to make their life decisions and behave autonomously and independently [11]. This type of parenting style is also presumed to be associated with social incompetence and lack of self control [12, 10].
In Nigeria, parenting strategies embrace all the three single parenting styles that has been described [10], with emphasis on obedience to authority and compliance with parental instructions [13]. This emphasis arises from the fact that, Nigeria being predominantly a hierarchical and patriarchal nation, the traditional society values respect for elders and authority figures and in particular parental authority in a family where the man is the head of the family. As a result many Nigerian parents demand for obedience to parental authority, and compliance with parental instructions from their children. However many of the parents accompany such demands for obedience and compliance with instructions, with responsiveness, love, care, sensitivity, reciprocal dialogue, and explanations for parental disciplinary actions. The combination of demand for obedience and responsiveness by parents allows Nigerian children to perceive their parents as authoritative some of the time and authoritarian at other times. This inference has been supported by research findings that indicated that authoritative and authoritarian parenting styles as well as their hybrids are significantly practiced by Nigerian parents [14, 13]
In Cameroon, child bearing is highly valued and beliefs and practices concerning child rearing vary by ethnic group. However certain values are commonly held by the ethnic groups. These values include the importance that the Cameroonians attach to learning by example and learning through play. They also attribute importance to observational learning by teaching their children to observe and imitate tasks performed by adults [15, 16]. It has been reported that the dominant family pattern in Cameroon is the patrilineal and extended or joint family [17]. This family pattern promotes interdependence, and the culture of the society is collectivistic and communal in orientation [4, 3]. The Cameroon parents (represented by Nso people in this write up, and who live in the Anglophone sector of Cameroon) engage in relationship-supporting parenting practices. These practices involve parental monitoring of children’s health, teaching life skills to the children and stimulating their growth and development [3, pp. 138]. Good parenting to this group of Cameroonians consists of parents taking the lead with monitoring, instructing, training, directing and controlling infants’ activities [3]. These parenting practices reflect a collectivistic society with an authoritarian parenting strategy.
On the other hand in a study carried out on cultural differences in parenting and infant’s socialization, in which two traditional farming community families ((Cameroon Nso families), & (India Gujarati Rajputs families)) and one western middle-class families (German families), were compared, it was found that parenting strategies in the two community families promoted communion [18]. Further, it was found that the Cameroonian and Indian infants were exposed to multiple caregivers and social cohesiveness within extended family networks. This finding further affirms the collectivistic and communal nature of the Cameroonian society. However, the results of the study also indicated that the socialisation strategy, used by Cameroon parents with their infants, was more indulgent (permissive) than that of the Indian parents. This second finding tends to portray the Cameroon parents as permissive and not authoritarian. It is however possible that these two parenting styles are actually being practiced by Cameroonian parents.
Deductions made from a study on family structure and juvenile delinquency [17], provided some insight into this possibility. According to these deductions, the traditional Cameroonian culture acknowledges and sanctions the authority of the father over his family but fails to specify a routine childcare role for him. The father therefore represents only an authority figure in the family but distant from his children, with a rigid attitude and emotional-non involvement posture. This father role omission created a gap between the high and lofty status and high esteem accorded the fathers in the culture and their appropriate and qualitative inputs needed for their children’s adequate development. In turn this gap was maintained by the societal attitude towards fathers who tend to be tender and nurturing towards their infants and young children, in that such fathers are either seen as effeminate or behaving inappropriately [19]. This societal position created confusion for the contemporary Cameroonian parents who struggle with the conflict between traditional and modern directives regarding parenting [17]. It was also asserted that the values of Cameroonian parents create the conditions that permit children to spend more time within the peer culture and less in the parent-child dyads [17]. As such most toddlers in Cameroon learn more from each other than from their parents or other adults, and the responsibility for the development of toddlers therefore falls less on parents and more on the children themselves or other children within the peer culture, [17, 20, 21-22].
From this indirect parental influence on the socialization of Cameroon children, it was inferred that Cameroonian parents especially fathers seemed to have evolved from being authoritarian and emotionally distant from their children to being permissive but still emotionally distant, (a situation in which control is now given over to children, with very few rules if any exist at all and these rules are inconsistently enforced, and where parents feel helpless or indifferent) [17]. He further stated that while the Cameroonian parents were struggling to preserve the traditional authoritarian parenting stereotype, they have been forced to become “unconsciously permissive” in their parenting style, which is tagged “indirect parental impact on children”, [17, 22]. This form of indirect parental influence on Cameroon children has been claimed to be effective, and effective because of a mechanism of self-regulation which exists within the peer culture and which is maintained by the power inherent in the expectations and directives of absent (authoritarian) parents whose direct intervention is no longer needed [22]. In essence the situation in the Cameroonian society seems to be that, in each family, there is the generation of an ambivalent father image which is “domineering” and “inaccessible” and which has “delegated the socialization process” to the peer culture. The deductions made and inferences arrived at, [17] have provided explanation for the dichotomy or ambivalence between the traditional authoritarian parenting stereotype seemingly adhered to by Cameroonian parents [3, pp138] and the prevailing permissive parenting strategy practiced by them especially mothers whose responsibility it is to nurture their infants and young children, [18]. The implication is that Cameroonian parents practice a form of permissive parenting strategy that is peer culture centred and driven by invisible and underlying authoritarian power of parents and promoted early in the children’s life by their mothers’ permissiveness. It is therefore expected that Cameroonian adolescents and young people would report authoritarian parenting style, permissive parenting style, and authoritarian/permissive parenting style hybrid as the parenting strategies adopted by their parents in bringing them up.
The design used for the studies reported here was cross sectional. The participants were assessed only once but at different times and different periods and from different locations and different schools. The sampling method used was convenience sampling based on availability of the participants.
The parenting style scale used for the studies being reported here is a 20 - item parenting style scale adapted from the parenting care scale, originally developed by Baumrind, (1971)[10]. The Baumrind’s parenting care scale that was available to the researcher and which was adapted consists of 20- items. Seven of the items (7) measures authoritarian parenting style, another seven (7) measures permissive parenting style, and the remaining six (6) measures authoritative parenting style. Response to Baumrind’s parenting care scale items is a “Yes” or a “No”. An internal consistency alpha coefficient of.86 was reported for this scale.
The adapted parenting style scale used for the studies reported here also consists of 20- items, but which contains items from Baumrind’s version and items from Rohner’s (1990) acceptance - rejection questionnaire [23]. In this scale, 5 of the items measures permissive parenting style, 6 items measures authoritarian parenting style while 9 items measures authoritative parenting style. In addition participants’ responses to the scale items in the adapted version varied according to the five point Likert Scale from strongly agree to strongly disagree on a scale of 1 to 5. This differs from the responses to the scale items in Baumrind’s version which is a “yes” or “no” response.
Examples of the items in the adapted scale include “My parents respects my privacy”, ”My parents really expects me to follow family rules”, “My parents give me a lot of freedom”. For the permissive parenting style, the number of items is five. If a respondent is uncertain for all the items his score would be 15. Therefore any score that is higher than 15 is taken as a permissive score. Consequently for authoritarian parenting style (6 items), any score that is higher than 18 is taken as an authoritarian score, and for authoritative parenting style (9 items) any score that is higher than 27 is taken as an authoritative score. For this adapted scale, the following correlation coefficients for a 5-week interval test retest reliability analysis were obtained: Permissive r = 0.67, authoritarian r = 0.35, Authoritative r = 0.80[24].
It is important to note here that the low test retest reliability coefficient for authoritarian parenting items may be explained on the following premise. Since Nigerian children’s perception of their parents’ parenting styles progresses and shifts towards authoritative parenting as they grow up, a shift in this direction might have occurred between the first test and the retest of the participants to the effect that it lowered the reliability of the authoritarian parenting items and increase the reliability of the authoritative parenting items at the retest point. This shift in perception is more likely because the reliability data was collected on Yoruba participants who tend to perceive their parents as more authoritative than authoritarian as they grow older. The implication then is that the reliability coefficient for authoritarian items may still be lower if samples that are older than the present sample is tested.
The participants were made up of 852 secondary school students from Ibadan a city in the South West of Nigeria and Ikom another city in the South East of Nigeria respectively. Of this sample, 585 students were from Ibadan, and 267 students were from Ikom. The students from Ibadan are from the Yoruba tribal group, and those from Ikom are from the Efik tribal group. There were 436 males and 416 females in the sample with their ages ranging between 11yrs and 24 yrs, and a mean age of 15.7yrs.
The convenience sampling method which was based on availability was employed in this study. Three research assistants who doubled as secondary school graduate teachers on national youth service assignments were recruited and requested to administer the questionnaires to the students in their respective schools in Ibadan, (South West, Nigeria) and Ikom, (South East Nigeria).
Behaviourally, the Yoruba tribal group demands respect for and obedience to authority figures and elders and they tend to believe that children are to be seen and not heard and to do as they are told. At the same time they demonstrate parental responsiveness and warmth by using behavioural and monitoring controls over their children by monitoring where they are, what they are doing and with whom they are because they are more family oriented and they value family integrity and dignity. Although they do not allow parent-child dialogue, they explain and give reasons for their disciplinary measures and actions. In this respect their children may perceive their parenting style as either authoritarian, or authoritative, or a mixture of both.
Behaviourally, the Efik tribal group are not as demanding of respect and obedience to authority figures as the Yoruba tribal group. This is because they tend to be more community oriented by organising themselves into community associations and ensuring regular and frequent meetings for cohesion and bonding, and they punish defaulters. The enforcement of community or tribal bonding and involvement may be perceived as authoritarian approach by members of the tribal group. It is therefore expected that young people of Efik decent would perceive the parenting style under which they were brought up as more authoritarian.
All the participants were secondary school students in their respective schools. As requested by their teachers, they completed a written questionnaire. The questionnaire contains three sections. The first section is a biographical information form. One of the remaining two sections contains measures of parenting style. Below are results of the parenting style section of the research.
Results:
\n\t\t\t\tParenting Styles\n\t\t\t | \n\t\t\t\n\t\t\t\tSample/Parenting style\n\t\t\t | \n\t\t\t\n\t\t\t\tX2\n\t\t\t\t\n\t\t\t | \n\t\t|
\n\t\t\t\tNo\n\t\t\t | \n\t\t\t\n\t\t\t\t%\n\t\t\t | \n\t\t||
Permissive | \n\t\t\t15 | \n\t\t\t1.6 | \n\t\t\t\n\t\t |
Authoritarian | \n\t\t\t72 | \n\t\t\t8.1 | \n\t\t\t2.42* | \n\t\t
Authoritative | \n\t\t\t381 | \n\t\t\t45.3 | \n\t\t\t8.35* | \n\t\t
Permissive & Authoritarian | \n\t\t\t11 | \n\t\t\t1.4 | \n\t\t\t\n\t\t |
Permissive & Authoritative | \n\t\t\t13 | \n\t\t\t1.4 | \n\t\t\t\n\t\t |
Authoritarian & Authoritative | \n\t\t\t248 | \n\t\t\t29.8 | \n\t\t\t5.41* | \n\t\t
Permissive/ Authoritarian/ Authoritative | \n\t\t\t31 | \n\t\t\t3.5 | \n\t\t\t\n\t\t |
Undifferentiated | \n\t\t\t81 | \n\t\t\t9.0 | \n\t\t\t2.51* | \n\t\t
Total | \n\t\t\t852 | \n\t\t\t100 | \n\t\t\t\n\t\t |
Distribution of Parenting styles and their hybrids
* Note: Critical X2 = 1.645, P<.05 Extracted from [14]
In table 1, the highest number of participants perceived their parenting style as authoritative (381 or 45.3%). This is followed by the hybrid combination of authoritarian/ authoritative style ( 248 or 29.8%). Undifferentiated parenting style hybrid followed with (81 or 9.0%), and then authoritarian parenting style with (72 or 8.1%). The chi-square values for these proportions are significant at P<.05. These are the parenting styles that had over 5% representation in the sample studied. These results indicate that adolescents and young people brought up under authoritative parenting style and the hybrid combination of authoritarian and authoritative parenting styles are significantly represented in the sample studied in this research.
\n\t\t\t\tParenting Styles\n\t\t\t | \n\t\t\t\n\t\t\t\t(Yoruba) No = 585\n\t\t\t | \n\t\t\t\n\t\t\t\t(Efik) No = 267\n\t\t\t | \n\t\t||
\n\t\t\t | No | \n\t\t\t% | \n\t\t\tNo | \n\t\t\t% | \n\t\t
Permissive | \n\t\t\t7 | \n\t\t\t0.90 | \n\t\t\t8 | \n\t\t\t0.70 | \n\t\t
Authoritarian | \n\t\t\t44 | \n\t\t\t4.90 | \n\t\t\t28 | \n\t\t\t3.10 | \n\t\t
Authoritative | \n\t\t\t289 | \n\t\t\t34.3 | \n\t\t\t92 | \n\t\t\t11.00 | \n\t\t
Permissive & Authoritarian | \n\t\t\t5 | \n\t\t\t0.70 | \n\t\t\t6 | \n\t\t\t0.70 | \n\t\t
Permissive & Authoritative | \n\t\t\t4 | \n\t\t\t0.40 | \n\t\t\t9 | \n\t\t\t0.90 | \n\t\t
Authoritarian & Authoritative | \n\t\t\t157 | \n\t\t\t18.50 | \n\t\t\t91 | \n\t\t\t11.30 | \n\t\t
Permissive/ Authoritarian/ Authoritative | \n\t\t\t19 | \n\t\t\t2.10 | \n\t\t\t12 | \n\t\t\t1.40 | \n\t\t
Undifferentiated | \n\t\t\t60 | \n\t\t\t6.60 | \n\t\t\t21 | \n\t\t\t2.40 | \n\t\t
Total | \n\t\t\t585 | \n\t\t\t68.66 | \n\t\t\t267 | \n\t\t\t31.34 | \n\t\t
Number & Percentages of Participants under each Parenting Style by Ethnic Groups (Extracted from [14])
\n\t\t\t\tParenting Styles\n\t\t\t | \n\t\t\t\n\t\t\t\tCross River (Efik) No = 267\n\t\t\t | \n\t\t\t\n\t\t\t\tOyo State (Yoruba) No = 585\n\t\t\t | \n\t\t\t\n\t\t | ||
\n\t\t\t | Mean | \n\t\t\tStd. Deviation | \n\t\t\tMean | \n\t\t\tStd. Deviation | \n\t\t\t“t” | \n\t\t
Authoritarian | \n\t\t\t18.73 | \n\t\t\t4.52 | \n\t\t\t17.57 | \n\t\t\t4.89 | \n\t\t\t3.29** | \n\t\t
Authoritative | \n\t\t\t31.52 | \n\t\t\t7.28 | \n\t\t\t33.07 | \n\t\t\t7.05 | \n\t\t\t- 2.94** | \n\t\t
Permissive | \n\t\t\t11.04 | \n\t\t\t3.87 | \n\t\t\t9.97 | \n\t\t\t3.41 | \n\t\t\t4.09** | \n\t\t
Means & Standard Deviations for Participants’ scores on Parenting Styles by Ethnic groups df = 849 **P<.01 (Extracted from [14])
Results in table 2 under the ethnic groups indicate that more participants of Yoruba decent perceived their parenting style as authoritarian, authoritative, and the hybrid combination of authoritarian/authoritative than participants of Efik decent. The results are: authoritarian: Yoruba – 44 or 4.9%, Efik– 28 or 3.10%; authoritative: Yoruba- 289 or 34.3%, Efik- 92 or 11%; authoritarian/authoritative combination: Yoruba- 157 or 18.5%, Efik- 91 or 11.3%.
The analysis presented in table 3 indicated that participants of Yoruba decent significantly perceived their parenting style as more authoritative, less authoritarian and less permissive, while participants of Efik decent significantly perceived their parenting style as more authoritarian, more permissive and less authoritative.
Participants in this study were made up of 352 students from a Private University in Ogun State, and a Federal University in Lagos State, both from the South Western part of Nigeria. The students from both universities were sampled on the basis of availability. They were undergraduate students studying psychology, and they were selected from 100 to 400 level. The ages of the participants ranged from 18 to 32 years. 144 of the participants were males and 208 were females. All the participants were full time students in their respective universities. The participants completed a written questionnaire that contained biographical information section and measures of parenting style, and some selected personality variables. Below are the results for the parenting style measure.
Results:
\n\t\t\t\tParenting Styles\n\t\t\t | \n\t\t\t\n\t\t\t\tNo/Parenting style\n\t\t\t | \n\t\t\t\n\t\t\t\t%\n\t\t\t | \n\t\t\t\n\t\t\t\tX2\n\t\t\t\t\n\t\t\t | \n\t\t
Authoritarian | \n\t\t\t32 | \n\t\t\t9.1 \n\t\t\t | \n\t\t\t2.51* | \n\t\t
Authoritative | \n\t\t\t215 | \n\t\t\t61.1 \n\t\t\t | \n\t\t\t10.37* | \n\t\t
Authoritarian & Authoritative | \n\t\t\t105 | \n\t\t\t29.8 \n\t\t\t | \n\t\t\t5.41* | \n\t\t
Total | \n\t\t\t352 | \n\t\t\t100.0 | \n\t\t\t\n\t\t |
Distribution of parenting styles and their hybrid
* Note: Critcal X2 = 1.645, P<.05 Extracted from [13]
In table 4 above, the highest number of participants (215, or 61.10%) fell under authoritative parenting style. This is followed by the hybrid combination of authoritarian and authoritative parenting style (105, or 29.80%). The next in number is authoritarian parenting style (32, or 9.10%). The chi-square values for these proportions were significant at P<.05. From this result, participants brought up under the three parenting styles were significantly represented in the sample studied. This result therefore validates an earlier documentation of the practice of the authoritarian and authoritative parenting style hybrid by Nigerian parents.
567 primary school children aged between 7 and 16 years selected from four primary schools in Yaba and Surulere areas of Lagos mainland in Lagos State participated in the study. Lagos State is located in the South Western part of Nigeria. The participants were made up of 275 male and 292 females. Three instruments namely, parenting style scale, children social anxiety scale and performance anxiety scale were administered to the children after ensuring that they understood the instructions and what they were expected to do. Below are the results for the parenting style measure.
Results:
\n\t\t\t\tParenting Styles\n\t\t\t | \n\t\t\tNo/Parenting style | \n\t\t\t% \n\t\t\t | \n\t\t\t\n\t\t\t\tX2\n\t\t\t\t\n\t\t\t | \n\t\t
Permissive | \n\t\t\t11 | \n\t\t\t1.9 | \n\t\t\t\n\t\t |
Authoritarian | \n\t\t\t13 | \n\t\t\t2.3 | \n\t\t\t\n\t\t |
Authoritative | \n\t\t\t\n\t\t\t\t79\n\t\t\t | \n\t\t\t14 \n\t\t\t | \n\t\t\t\n\t\t\t\t3.92*\n\t\t\t | \n\t\t
Permissive & Authoritarian | \n\t\t\t19 | \n\t\t\t3.4 | \n\t\t\t\n\t\t |
Permissive & authoritative | \n\t\t\t\n\t\t\t\t37\n\t\t\t | \n\t\t\t6.5 | \n\t\t\t\n\t\t |
Authoritarian & Authoritative | \n\t\t\t\n\t\t\t\t273\n\t\t\t | \n\t\t\t48.3 \n\t\t\t | \n\t\t\t\n\t\t\t\t8.54*\n\t\t\t | \n\t\t
Permissive/Authoritarian/Authoritative | \n\t\t\t\n\t\t\t\t113\n\t\t\t | \n\t\t\t20.0 \n\t\t\t | \n\t\t\t\n\t\t\t\t4.75*\n\t\t\t | \n\t\t
Undifferentiated | \n\t\t\t20 | \n\t\t\t3.5 | \n\t\t\t\n\t\t |
Total | \n\t\t\t565 | \n\t\t\t100 | \n\t\t\t\n\t\t |
Distribution of parenting styles and their hybrids in the Sample
* (Note: Chi-square table values are: (x2 =1.96 P<.05); Extracted from [25]
From table 5 above, out of 565 participants 273 or 48.3% of the children reported being brought up under the authoritative/authoritarian parenting style hybrid. The chi-square (x2) value for this proportion is 8.54 and it is significant at P<.05. Similarly out of 565 children studied 79 of them or 14% reported being brought up under authoritative parenting style. The chi-square (x2) value for this proportion is 3.92 and it is also significant at P<.05. In addition out of the 565 children who participated in this study, 113 or 20% of them reported being brought up under the permissive/authoritative/authoritarian parenting style hybrid. The chi-square (x2) value for this proportion is 4.75 and it is also significant at P<.05. These results further confirm that a significant number of Nigerian parents as perceived by their children, practice the authoritarian/authoritative parenting style hybrid. In addition the children in this study perceived a significant number of their parents to also be practicing another hybrid, the permissive/authoritarian/authoritative parenting style.
668 primary and junior secondary school children aged between 7 and 13 years selected from three primary and three junior secondary schools on Lagos mainland in Lagos State participated in the study. Lagos State is one of the States situated in the South Western part of Nigeria. The participants were made up of 281 males and 387 females. The children were administered five measuring instruments namely, parenting style scale, Nigerian Children’s self concept scale, self esteem scale, locus of control scale, and sense of competence scale. The measures were administered to the children after ensuring that they understood the instructions and what they were expected to do. In addition the children were guided while responding to the measures by four research assistants employed to assist in carrying out the study. Below are the results for the parenting style measure.
\n\t\t\t\tParenting style\n\t\t\t | \n\t\t\t\n\t\t\t\tNo/Parenting style\n\t\t\t | \n\t\t\t\n\t\t\t\t%\n\t\t\t | \n\t\t\t\n\t\t\t\tX2\n\t\t\t\t\n\t\t\t | \n\t\t
Permissive | \n\t\t\t1 | \n\t\t\t0.15 | \n\t\t\t\n\t\t |
Authoritarian | \n\t\t\t14 | \n\t\t\t2.10 | \n\t\t\t\n\t\t |
Authoritative | \n\t\t\t122 | \n\t\t\t18.26 | \n\t\t\t\n\t\t\t\t4.45*\n\t\t\t | \n\t\t
Permissive/Authoritarian | \n\t\t\t6 | \n\t\t\t0.90 | \n\t\t\t\n\t\t |
Permissive/Authoritative | \n\t\t\t23 | \n\t\t\t3.44 | \n\t\t\t\n\t\t |
Authoritarian/Authoritative | \n\t\t\t410 | \n\t\t\t61.38 | \n\t\t\t\n\t\t\t\t10.48*\n\t\t\t | \n\t\t
Permissive/Authoritarian/ Authoritative | \n\t\t\t84 | \n\t\t\t12.57 | \n\t\t\t\n\t\t\t\t3.25*\n\t\t\t | \n\t\t
Undifferentiated | \n\t\t\t8 | \n\t\t\t1.20 | \n\t\t\t\n\t\t |
Total | \n\t\t\t668 | \n\t\t\t100 | \n\t\t\t\n\t\t |
Distribution of Parenting styles and their hybrids in the sample
* Note: Critical X2 =1.96, P<.05; table extracted from[26]
From the results in table 6 above 410 or 61.38% of the children reported being brought up under the authoritarian/authoritative parenting style hybrid, 122 or 18.26% reported being brought up under authoritative parenting, and 84 or 12.57% reported being brought up under the hybrid combination of the three parenting styles. The chi-square values for these three proportions were significant at P<.05. The results in table 6 again confirm that Nigerian parents do regularly practice the parenting styles significantly represented in the sample.
It is necessary to note at this point that some consistencies have been recorded in the outcome of the studies. For example in the first two studies (study 1 and study 2) where the participants were adolescents and young people, the highest proportion of them ( e.g. 45.3%, 61.1%), reported being brought up under authoritative parenting. This was followed by the authoritarian/authoritative parenting style proportion of (29.8%, 29.8%) respectively. In study 3 and study 4 where the children that participated in the research were younger, the highest proportion of them reported being brought up under the authoritarian/authoritative parenting style hybrid (e.g. 48.3%, 61.38%) respectively. The next higher proportion in study 3 is the hybrid that combines the three single parenting styles which is (20%), and this is followed by the proportion for the authoritative parenting style (14%). For study 4 the next higher proportion is for the authoritative parenting which is (18.26%), and which is followed by the proportion of the combination of the three single parenting styles hybrid. One deduction that can be made from these results is that for Nigerian children when they are young dominantly perceive their parents’ parenting styles as a combination of authoritarian and authoritative parenting style. As they grow older they begin to see their parents as more authoritative and less authoritarian. The next study reported below compares the parenting styles of Nigerian parents with that of Cameroonian parents.
The participants were made up of 355 secondary school students from Lagos and Ibadan cities in Nigeria, and 156 college students from Bamenda in Cameroon. There were 221 males and 290 females in the sample and their ages ranged between 13 and 27years.The participants responded to questionnaires on parenting style and sexual attitude. Results for the distribution of the parenting styles are presented below:
\n\t\t\t\tParenting styles\n\t\t\t | \n\t\t\tNigeriaNo of Participants = 355 | \n\t\t\tCameroonNo of Participants = 156 | \n\t\t\tTotal SampleNo of Participants =511 | \n\t\t||||||
\n\t\t\t | \n\t\t\t\tNo\n\t\t\t | \n\t\t\t\n\t\t\t\t%\n\t\t\t | \n\t\t\t\n\t\t\t\tX2\n\t\t\t\t\n\t\t\t | \n\t\t\t\n\t\t\t\tNo\n\t\t\t | \n\t\t\t\n\t\t\t\t%\n\t\t\t | \n\t\t\t\n\t\t\t\tX2\n\t\t\t\t\n\t\t\t | \n\t\t\t\n\t\t\t\tNo\n\t\t\t | \n\t\t\t\n\t\t\t\t%\n\t\t\t | \n\t\t\t\n\t\t\t\tX2\n\t\t\t\t\n\t\t\t | \n\t\t
Permissive | \n\t\t\t- | \n\t\t\t- | \n\t\t\t- | \n\t\t\t85 | \n\t\t\t54.5 | \n\t\t\t\n\t\t\t\t9.47*\n\t\t\t | \n\t\t\t85 | \n\t\t\t16.63 | \n\t\t\t\n\t\t\t\t4.20*\n\t\t\t | \n\t\t
Authoritarian | \n\t\t\t15 | \n\t\t\t4.23 | \n\t\t\t- | \n\t\t\t2 | \n\t\t\t1.28 | \n\t\t\t- | \n\t\t\t17 | \n\t\t\t3.33 | \n\t\t\t- | \n\t\t
Authoritative | \n\t\t\t151 | \n\t\t\t42.5 | \n\t\t\t\n\t\t\t\t8.11*\n\t\t\t | \n\t\t\t1 | \n\t\t\t0.64 | \n\t\t\t- | \n\t\t\t152 | \n\t\t\t29.75 | \n\t\t\t\n\t\t\t\t5.40*\n\t\t\t | \n\t\t
Permissive/ Authoritarian | \n\t\t\t4 | \n\t\t\t1.13 | \n\t\t\t- | \n\t\t\t49 | \n\t\t\t31.4 | \n\t\t\t\n\t\t\t\t5.72*\n\t\t\t | \n\t\t\t53 | \n\t\t\t10.37 | \n\t\t\t\n\t\t\t\t3.82*\n\t\t\t | \n\t\t
Permissive/ Authoritative | \n\t\t\t4 | \n\t\t\t1.13 | \n\t\t\t- | \n\t\t\t8 | \n\t\t\t5.13 | \n\t\t\t- | \n\t\t\t12 | \n\t\t\t2.35 | \n\t\t\t- | \n\t\t
Authoritarian/ Authoritative | \n\t\t\t147 | \n\t\t\t41.4 | \n\t\t\t\n\t\t\t\t8.01*\n\t\t\t | \n\t\t\t- | \n\t\t\t- | \n\t\t\t- | \n\t\t\t147 | \n\t\t\t28.77 | \n\t\t\t\n\t\t\t\t5.11*\n\t\t\t | \n\t\t
Permissive/ Authoritarian/ authoritative | \n\t\t\t13 | \n\t\t\t3.66 | \n\t\t\t- | \n\t\t\t3 | \n\t\t\t1.92 | \n\t\t\t- | \n\t\t\t16 | \n\t\t\t3.13 | \n\t\t\t- | \n\t\t
Undifferentiated | \n\t\t\t21 | \n\t\t\t5.92 | \n\t\t\t- | \n\t\t\t8 | \n\t\t\t5.13 | \n\t\t\t- | \n\t\t\t29 | \n\t\t\t5.68 | \n\t\t\t- | \n\t\t
Total | \n\t\t\t355 | \n\t\t\t100 | \n\t\t\t- | \n\t\t\t156 | \n\t\t\t100 | \n\t\t\t- | \n\t\t\t511 | \n\t\t\t100 | \n\t\t\t- | \n\t\t
Distribution of Parenting styles and their hybrids for Nigeria and Cameroon Samples
* Note: (Critical value of X2 = 1.96 P<.05) table extracted from [27]
From the results in table 7, 151, (42.5%) Nigerian respondents reported being brought up under authoritative parenting strategy, and 147, (41.4%), reported being brought up under the authoritarian/authoritative parenting style hybrid. 85 (54.5%) Cameroonian respondents reported being brought up under permissive parenting, and 49 (31.4%) reported being brought up under the permissive/authoritarian parenting style hybrid. The chi-square values for these proportions are significant at P<.05. These results indicate therefore that the dominant parenting styles adopted by Nigerian parents are the authoritative parenting style and the authoritarian/authoritative parenting style hybrid. Furthermore the results indicate that the dominant parenting styles adopted by Cameroonian parents are the permissive parenting style and the permissive/authoritarian parenting style hybrid.
The results for Nigerian samples in table 7 are consistent with earlier findings in studies (1-4) reviewed above and further confirm the authoritative/authoritarian parenting style hybrid and the authoritative parenting style as the parenting styles being actively practiced by Nigerian parents. From the results in studies 3 and 4 above (tables 5 and 6) it can be deduced that Nigerian parents are evolving by progressing from being authoritarian and authoritative simultaneously to being authoritative and this may be the reason why the authoritarian/authoritative parenting style hybrid had highest proportions when the children were younger ( e.g. tables 5 and 6), and authoritative parenting style had highest proportions when the respondents were older.
For Cameroonian sample the results in table 7 that indicated that Cameroonian parents are predominantly permissive (e.g. 54.5% of sample), agrees with Ngale’s deduction that the Cameroonian parenting style that puts the responsibility of parenting on the peer culture is permissive and that the stereotypic traditional authoritarian parenting style they so claim to be practicing has become dysfunctional or at best superficial. On the other hand the second dominant parenting style of permissive/authoritarian parenting style hybrid (31.4% of the sample) documented in this study, supports the notion of the power inherent in the expectations and directives of absent (authoritarian) parents, the power which enforces and maintain self-regulation within the peer culture, [22]. The implication here is that Cameroonian parents actively practice permissive parenting style as well as the permissive/authoritarian parenting style hybrid. The scores of the participants on the three single parenting styles were analysed and compared. The results are presented in table 8 below:
\n\t\t\t\tParenting Style\n\t\t\t | \n\t\t\tNigeriaNo of Participants = 355 | \n\t\t\tCameroonNo of Participants = 156 | \n\t\t\tT calculated“t” | \n\t\t\t\n\t\t\t\tP\n\t\t\t | \n\t\t||
\n\t\t\t | \n\t\t\t\tMean\n\t\t\t | \n\t\t\t\n\t\t\t\tStd. Dev.\n\t\t\t | \n\t\t\t\n\t\t\t\tMean\n\t\t\t | \n\t\t\t\n\t\t\t\tStd. Dev.\n\t\t\t | \n\t\t\t\n\t\t\t | \n\t\t |
Permissive | \n\t\t\t9.76 | \n\t\t\t3.43 | \n\t\t\t20.30 | \n\t\t\t5.61 | \n\t\t\t26.05 | \n\t\t\tP<.05 | \n\t\t
Authoritarian | \n\t\t\t17.81 | \n\t\t\t5.12 | \n\t\t\t20.64 | \n\t\t\t3.87 | \n\t\t\t6.17 | \n\t\t\tP<.05 | \n\t\t
Authoritative | \n\t\t\t33.19 | \n\t\t\t7.21 | \n\t\t\t16.86 | \n\t\t\t4.01 | \n\t\t\t- 26.55 | \n\t\t\tP<.05 | \n\t\t
Parenting style mean scores for Nigerian and Cameroon participants (Extracted from [27])
From table 8 above it can be seen that Nigerian participants scored significantly higher than Cameroonian participants on authoritative scale indicating that Nigerian parents are more authoritative in their parenting strategy than Cameroonian parents. On the other hand Cameroonian participants scored significantly higher than Nigerian participants on permissive and authoritarian parenting scale. This indicates that Cameroonian parents are more permissive and authoritarian in their parenting approach than Nigerian parents. However the authoritarian parenting style being practiced by Cameroonian parents are indirect and invisible. The findings also agree with the findings of [18], that reported permissive parenting practices among Cameroonian parents on the one hand and report of Cameroonian parents’ belief in and adoption of authoritarian parenting strategy on the other hand [3].
The importance of studying parenting practices is (i) to determine the nature, and variety of practices that parents adopt while bringing up their children, and (ii) to examine the effectiveness and benefits of such practices. From the reviewed literature, “ see [18, 7], and the studies reported here, it can be deduced that parental practices vary from one culture to another culture and such practices reflect the cultural values of the society. Nigeria is a collectivistic and patriarchal society with values such as obedience to authority figures, compliance with parental instructions, cooperation and helpfulness within and outside the extended family systems, communal living and good interpersonal relationship. According to the studies reported here, the Nigerian parents practice dominantly authoritative parenting style and the hybrid authoritarian/authoritative parenting style. Cameroon is also a collectivistic and patrilineal society that values communal living, extended family system and observational learning, learning through play and interaction with peers, and from the findings reported here, the Cameroonian parents dominantly practice permissive parenting style and the permissive/authoritarian parenting style hybrid. Although Nigeria and Cameroon are collectivistic societies, they still practice different parenting styles and the parenting styles being practiced by these two collectivistic Countries must have been effective in achieving their parenting goals. It has been found in a study that young people (Nigerians), brought up under authoritative parenting, authoritarian parenting, and the authoritative/authoritarian parenting hybrid were not significantly different in their levels of sense of competence, need for achievement, locus of control, and academic achievement. However participants brought up under authoritative parenting style reported the highest level of self esteem when compared to other parenting styles, [13]. These results indicate that the three parenting strategies are equally effective for Nigerian parents. In the same way it was found that the Nigerian and Cameroonian participants were not statistically different in their restraint, liberal and permissive attitudes towards sexuality issues, and interestingly the Cameroonian participants reported significantly higher judgemental attitude and attitude toward parental responsibility with respect to sexuality issues, [27]. This finding implies that the parental strategies being practiced by Cameroonian parents are effective in achieving their parenting goals. A broader implication of these findings is that parenting styles adopted by a group is a function of the values upheld by the group and the goals of parenting of that group. Besides, a number of studies have demonstrated that different parental strategies work for different groups in different cultural contexts. For example some studies have demonstrated the beneficial effects of authoritative parenting both in individualistic and collectivistic cultures, see [28, 29, 13], while some other studies have also demonstrated the beneficial effects of authoritarian parenting especially in collectivistic cultures, see [7, 30, 31, 13]. Even the permissive parenting style which is associated with negative outcomes, [32], just like authoritarian parenting style, [11], has also been found to be effective in bringing positive child outcomes for Cameroonian parents, [27]. The general conclusion that can be drawn from all these studies is that parenting style as a global construct reflects the quality of parent-child relationships which varies from one cultural context to another and which is driven by the cultural beliefs, values, and practices of the particular culture. As suggested, see [8], when parenting behaviour is consistent with cultural values then the children in that culture will accept it. It therefore follows that in the countries or societies in which authoritative, authoritarian and permissive parenting styles bring about positive child outcomes, parental behaviours must have been consistent with the cultural values of such countries. In addition whether a particular parenting style produces positive or negative child outcomes would depend on the culture within which it is practiced.
Finally it would be interesting if future researchers can explore the possibility of the existence of hybrids of the three single parenting styles in other cultures beside Nigeria and Cameroon which has been documented.
Since the discovery of induced pluripotent stem cells (iPSCs) by Yamanaka and Takahashi in 2006, many expectations have emerged, and iPSCs have opened up a world of possibilities for new cell-based therapies in regenerative medicine [1]. In the domain of pluripotent stem cells, iPSCs are considered as equivalent to embryonic stem cells (ESCs), because of two intrinsic key properties: their indefinite proliferative capacities while preserving pluripotency and their capacity to differentiate into all known cell types. However, in contrast to ESCs, iPSCs can be generated without any controversial ethical issues, thus favoring their use in clinical settings. Last but not least, in an autologous approach of cell-based therapy, by using the patient’s own cells as source for iPSC generation, one circumvents all the issues related to the immunological compatibility between the donor and receiver. This largely explains the tremendous enthusiasm engendered by iPSC discovery in the sphere of regenerative medicine during the last decade. In this review article, we provide an overview of the launched clinical trials with iPSC and the ongoing efforts to understand the risk related to safety of iPSC-derived cells, highlighting some of the problems that have to be overcome.
After over a decade of research on iPSC, and due to fast-track facilitating procedure in Japan, several clinical studies were launched. While the first clinical trial based on the human ESC started in 2010, taking advantage of the acquired extensive knowledge of ESC biology, despite their relatively recent discovery, the first clinical study based on the iPSC-derived retinal pigmented epithelium was authorized and conducted at the RIKEN Institute in Japan in 2014 [2]. A sheet of autologous iPSC-derived retinal cells were transplanted in a patient with eye-related macular degeneration (AMD). In 2015, the RIKEN Institute decided to suspend the study due to safety concerns on the cells of the second recruited patient [3]. Nonetheless, regarding the first transplanted patient, a 25-month follow-up revealed neither serious events, nor clinical signs of rejection. Moreover, the macular degeneration progress was delayed in the treated eye compared to the untreated eye. This result corroborated all the results obtained previously in the course of the ESC-based clinical studies, where no adverse events related to transplanted cells were observed. Still this problem induced a shift in the approach from patient-specific autologous to highly securized allogeneic iPSC lines. This study was resumed in 2017 and until now five patients with AMD have been treated with allogeneic iPSC-derived cells.
Since then, several clinical studies based on allogeneic iPSCs have been developed and approved. Until mid-2019, there have been nine ongoing clinical studies based on iPSC, mostly nationally approved in Japan, with four of them being approved in the first months of 2019, with indications including Parkinson’s disease, AMD, severe cardiac failure, aplastic anemia, spinal cord injury and corneal stem cell deficiency. Furthermore, two private companies—Cynata Therapeutics, an Australian stem cell and regenerative medicine company, and Fate Therapeutics, an American clinical-stage biopharmaceutical company—have developed a line of products based on allogeneic human iPSC-derived cells. In Australia and United Kingdom, Cynata Therapeutics just concluded a phase I study using CYP-001, an iPSC-derived mesenchymoangioblast precursor administered intravenously in 15 patients with graft-versus-host disease (GVHD) occurring after an allogeneic hematopoietic stem cell transplant [4]. Currently, all patients treated so far have demonstrated at least a partial response, while no treatment-related serious adverse events or safety concerns have been observed. The product development activities of CYP-001 will be done in a phase II study in 2019 by Fujifilm in collaboration with Cynata Therapeutics. On its part, Fate Therapeutics received a first approval from Food and Drug Administration (FDA) in November 2018 to transplant an off-the-shelf iPSC-derived Natural Killer cell, FT-500, as cancer immunotherapy to treat solid tumors and for a second cell product derived from a genetically engineered iPSC, FT-516, in February 2019, for the treatment of relapsed/refractory hematologic malignancies. For the first product FT-500, all the three patients with advanced solid tumors have been treated with multiple doses of FT-500, 100 million cells per dose, and it has been well tolerated with no dose-limiting toxicities or adverse events [5].
Even though the first clinical studies have already been started, technical advances in iPSC biology have revealed that several factors could affect their safety for a larger range of medical applications, and should be taken into account for short- and long-term follow-up of patients. Two of the major concerns related to iPSC-based products are their potential tumorigenicity and immunogenicity. The scientific community is still continuing to elucidate the biological mechanisms underlying iPSC’s immunogenicity and tumorigenicity and how to manage or overcome them.
The potential risk of tumorigenicity to patients from both teratomas and malignant tumors could arise if transplanted cells are contaminated with undifferentiated iPSC, or if transplanted cells have been genetically modified and become unstable during the in vitro production steps.
The major concern related to iPSC-based tumorigenicity is the reprogramming method. In the original cocktail of transcription factors developed by Yamanaka, somatic cells are transduced by retroviral vectors that become integrated into the genome of the host cells. Two of these factors—c-Myc and klf4—are potent oncogenes [6]. Subsequently, reports of tumorigenicity after transplantation of iPSC or iPSC-derived cells are not surprising. Thereby, teratoma formation could be induced by the undesired activation/suppression of essential host genes proximal to integration sites or by residual expression of reprogramming factors in the derived cells in animal model [7, 8]. With hindsight, there is evidence for the necessity to select a non-integrative method for reprogramming, a higher rate of genomic alterations occurring when human iPSCs are generated with viral vectors, compared to mRNA [7, 9]. Numerous studies, focused on the choice of reprogramming factors and methods of delivery, have developed various novel strategies to enhance the efficiency of reprogramming and reduce the potential risk of tumorigenicity. To circumvent this risk, human iPSCs have been generated by several “integration-free” methods, based on the use of viral vectors (adenoviral vectors and Sendai virus-based vectors) or non-viral vectors (piggyBac system, minicircle vector, and episomal vectors). Originally, the four transcription factors needed for complete cell reprograming were c-myc, klf4, oct4 and sox2 [1]. The pro-tumorigenic transcription factor c-myc has been found to be unnecessary for the reprogramming process, but the overall efficiency is decreased without it. Several strategies have been developed with the use of different transcription factors and/or replacement of c-myc, or the use of direct protein delivery and synthesized mRNA [10, 11, 12].
Furthermore, the tumorigenicity risk is often linked to the genetic instability of iPSC. Random genomic alterations are frequently observed in human iPSCs showing their intrinsic instability, essentially due to the massive genome remodeling, and probably also resulting from various mechanisms such as replicative stress, reactivation of the telomerase and metabolism modification from the oxidative to the glycolytic state. Epigenetic modifications may also contribute to iPSC variation due to residual epigenetic memories of the starting cell type [13]. The incomplete resetting of the non-CpG methylation patterns during reprogramming leads to a biased differential potential in certain cell types depending on the donor cell source [14, 15]. However, it has been shown that their residual epigenetic memory diminishes with the in vitro expansion over a period of time [16, 17]. As just mentioned, the selection of the donor cell type is of importance. Many human somatic cell types have been successfully reprogrammed. However, even if the use of different transcription factors, delivery methods and culture conditions does not facilitate any comparison, it is well known that reprogramming efficiencies, kinetics and tumorigenicity vary between somatic cell types. Firstly, cell sources have to be permissive to avoid to turn to integrative methods and to the use of oncogenes. Some human, adult somatic cells, such as melanocytes, are known to naturally express endogenously reprogramming factors, for instance Sox 2, at sufficiently high levels [18, 19]. Moreover, some types of donor cells such as dermal fibroblasts and blood cells are easily accessible, but they might carry more mutational burdens and chromosomal abnormalities, due to their frequent exposure to environmental stress factors, like ultraviolet rays, or due to the donor’s age, thereby leading to increased tumorigenicity, and significant safety problems [20, 21]. With all these considerations of cell variability and tumorigenic potential in mind, reflection on the generation of homogeneous cell source and banking emerged.
Many approaches have been evaluated to address the tumorigenicity challenge by eliminating the pluripotent cells of the final product such as small molecule, genetic approach to introduce a suicide gene; miRNA switch; antibodies targeting a surface-specific antigen; phototoxic approach; live detection and quantification of the residual human iPSC [22]. For the suicide gene approach, the most widely used gene is herpes simplex virus thymidine kinase (HSV-TK) that phosphorylates ganciclovir (GCV) and induces apoptosis by inhibiting DNA synthesis. Many studies demonstrated its efficacy as safeguard to eliminate tumoral cells [23]. Until then, this genetic approach with an inducible suicide system may remain not necessary enough to induce tumor elimination because of potential acquired resistance to GCV due to variability of insertion location sites and to the uncontrolled number of inserted transgene [24]. Another study demonstrated the same mechanism of inducing apoptosis in 95% of iPSCs and iPSC-derived cells by transducing an inducible Caspase 9 [25]. Recently, with development of targeted genetic strategies such as gene-editing, researchers try to identify the location of “genomic safe harbors” (GSH), corresponding to the safest permissive loci for transgenes’ insertion [26]. The already known GSH candidates could be AAVS1 (adeno-associated virus integration site 1), CCR5 (chemokine CC motif receptor 5), human ROSA26 and some extragenic loci. Recently, to predict the influence of gene integration on nearby genes, it has been suggested that the combination of several distinct approaches such as the analysis of the topologically associated domains of GSH candidates of chromosomes could reduce the risks associated with cell therapy [27]. Another targeted alternative, eliminating selectively residual pluripotent cells sparing precursors and differentiated cells, involves PluriSIns, pluripotent cells-specific inhibitors [28]. Alternatively, antibody, lectin or miRNA-mediated removal undesired cells were developed to suppress the pluripotent stem cells from the final product [29]. Lastly, a novel methodology using synthetic microRNA switch is developed to improve the purity of the final product even if the cell surface markers are not available to tag the relevant cells [30, 31].
The immunogenicity of differentiated cells derived from iPSC is of clinical significance. At the beginning, because of the use of the patient’s own cells, theoretically there is no risk of rejection after their transplantation. Some studies demonstrated no immune rejection of autologous iPSC-derived cells, but an activated immune response after the use of allogeneic iPS derived cells. Contrarily, immune rejection has been observed after autologous transplantation of iPSC-derived cells, suggesting that in vitro operations could also impact on the immunogenicity of the iPSC [32]. Moreover, the immune response to undifferentiated iPSC is different from their derivatives, emphasizing the need to perform similar comparative analyses in starting cell populations in order to predict immune tolerance after transplantation. Whereas autologous hiPSC-derived smooth muscle cells were highly immunogenic, autologous hiPSC-derived retinal pigment epithelial (RPE) cells were immune tolerated, suggesting a potential abnormal expression of some immunogenic antigens in smooth muscle cells [33]. These results demonstrated that the nature of the differentiated cells could trigger an immune response suggesting the importance of the differentiation protocol.
As mentioned earlier, because of their genomic instability, generation, amplification and differentiation of iPSC could induce a modified immune response of the iPSC in vivo. Concerning reprogramming, the RNA-based methods are relatively efficient and do not integrate in the genome, but they are also known to be highly immunogenic. Concerning cell type, it has been widely shown that iPSCs could be generated from a patient’s own cells including fat cells, nerve cells, skin fibroblasts, cuticle cells, fetal foreskin cells, B cells, T cells, peripheral blood mononuclear cells, umbilical cord mesenchymal cells, chorionic mesenchymal cells and amniotic mesenchymal cells. But, some studies showed that the genetic memory of the cellular immunogenicity is conserved after reprogramming and differentiation. So, the selection of donor cell type/origin is crucial. As an example, iPSCs derived from less immunogenic cells, such as umbilical cord mesenchymal cells, generated less immunogenic neural derivatives than those from skin fibroblasts-derived iPSCs [34]. Recently, several researchers showed the less immunogenic potential of some iPSC-derived cells as cartilage and retinal pigment epithelium cells when they are implanted in vivo, arguing that some cell types are less immunogenic and should be preferred for clinical settings [35, 36].
Recently, a novel approach of “Universal” iPSC was developed to address the difficulty of immunogenicity of allogeneic iPSCs. Hypoimmunogenicity of iPSC was induced by inactivation of major histocompatibility complex class I and II genes and overexpression of CD47 enabled them to escape to immune rejection in fully HLA-mismatched allogeneic recipients. This strategy allowed the long-term survival of the transplanted cells without the use of immunosuppression. However, overexpression of CD47 is associated with malignant transformation, leading to include some suicide strategies as a safety concern [37]. These immune escape approaches open the door to the clinical use of allogeneic iPSC-derived cell products without immune rejection concerns and complications. However, their complex production process including a combination of several transduction and gene-editing operations could add many safety issues. Even though other vectors and gene-editing techniques [38, 39] could also be used to reduce the risks, the multiple genetic manipulations and additional expansions in culture require a reinforced control of the “Universal” iPSC quality for clinical settings.
The use of human iPSCs in medicinal applications requires the establishment of standardized and validated protocols that will allow large-scale, cost-effective cultivation procedure, while maintaining their quality. Implementation of good manufacturing practice (GMP)-compliant protocols for the generation and maintenance of human iPSC lines is crucial to increase the application safety and to fulfill the regulatory requirements to obtain clinical trials’ approval. Many efforts to increase the overall iPSC stability, reproducibility and quality have been performed by (1) selecting the cell type that is easily accessible, less immunogenic, and permissive for reprogramming and presents the ability to be stored for longer periods of time; (2) improving reprogramming efficiency, which should be as high as possible without genomic integration-based delivery method and without using oncogene and (3) improving cultivation methods with xeno- and feeder-free products, with defined and scalable conditions for maintenance and differentiation of human iPSC such as automation, closed cell systems and validated protocols [40]. Moreover, selection of cell source is of importance. Demonstration of comparability, standardization and validation of such systems is critical for iPSC-derived therapies. To circumvent and manage the safety risk of the iPSC for regenerative medicine, several groups worked at the early stage on the development of standardized clinical grade iPSC banks from allogeneic donors. Indeed, the use of highly defined iPSC as starting cells presents many advantages as overcoming the genetic variations inducing different immunogenicity, genetic instability, tumorigenicity, and differentiation outcomes. Moreover, generation of iPSC from each patient is costly and time-consuming. In this regard, several groups in the world have developed banking of allogeneic iPSC lines for clinical use with validated and standardized protocols. The possibility of creating off-the-shelf iPSC-based therapies has attracted not only academics but also industrial groups as Lonzo and Cellular Dynamics International, a Fujifilm company.
iPSC banks can provide a cost-effective mass-production strategy. Several groups have developed iPSC banks from selected HLA donors trying to cover the majority of the population [41, 42]. The Center for iPSC Research and Application (CiRA), in Kyoto University, started the iPS Cell Stock for Regenerative Medicine in 2013. Initially, based on the limited diversity of the Japanese population, CiRA wanted to generate clinical-grade iPSCs from samples of peripheral blood and umbilical cord blood from healthy selected donors that would cover 90% of Japanese population with only 50 iPSC lines [43]. This strategy is valuable for countries such as Japan, but could be difficult to expand to the worldwide population. It has been evaluated that a multiethnic iPSC bank of the 100 most common HLA types in each population would cover only 78% of European individuals, 63% of Asians, 52% of Hispanics and 45% of African Americans [44]. This probabilistic model highlights the necessity of a large-scale international collaboration for the constitution of haplobank of iPSC lines. Using HLA-homozygous donors limits the numbers of iPSC lines needed to cover a given population, but identification of the potential donors would need large screenings or the use of established data from cord blood banks. The potential development of “universal” iPSCs made of genetically modified cells offering an off-the-shelf product that is readily available could be an alternative to the iPSC bank using materials from HLA-homozygous donors. The “universal” iPSC could solve the problem of immune rejection profile of iPSC-derived cells by artificially expressing, for example, HLA molecule as HLA-E allowing iPSC-derived cells to escape T cell-mediated rejection and to be resistant to NK-cell lysis [37, 45].
Nevertheless, stochastic events potentially occurring during reprogramming, colony expansion, iPSC selection, differentiation, iPSC-derived cell expansion and purification, storage and transport could complicate efforts toward a standardized product. Consequently, it has to be taken into consideration that variation may exist within any iPSC bank, between iPSC and final product composed of iPSC-derived cells in the clinic. Such variability requires continual extensive genotypic, phenotypic and functional assessment and highlights the need of a global quality control confirming the iPSC and the iPSC-derived cells’ quality whatever the manufacturer, the reprogramming method or the cell donors.
Given the high variability across iPSC lines and their differentiated derivatives in terms of their epigenetic status, tumorigenic and immunogenic potential, differentiation capacity, batch variability and existence of heterogeneous populations and/or non-relevant cells such as contaminating cell, the clinical outcome of the cell replacement therapy, in terms of efficacy and safety with these iPSC-based products, highly relies on the acceptable quality and safety standards of these products. Because of dissimilarities between institutions on these criteria, agreement on the critical quality attributes (CQAs) of such lines and the assays that should be used is required. The CQAs correspond to the chemical, physical and biological properties of the product. As well as the type of assay, they have to be defined within an appropriate limit, range or distribution to ensure quality and safety of the product. For cell therapy product and for clinical-grade iPSC, the CQAs include identity, microbiological sterility, genetic fidelity and stability, viability, characterization and potency. In the last few years, there was a common effort made on the banking and the quality control of the iPSC lines. After a series of workshop, adaptation to iPSC of the established recommendations and guidance realized by the International Stem Cell Banking Initiative (ISCBI) for human embryonic stem cell banking, has generated initial recommendations on the minimum dataset required to consider an iPSC line of clinical grade [46]. During these workshops, the researchers, industrial and regulation agencies pointed out the requirement of standardization and validation of process and quality and safety controls. For each criterion, one or several tests are required with regard to the recommended analytical methods. Global consensus recommends the performance of assays by accredited and licensed laboratories. When it is not available, in-house tests should be undertaken after validation and qualification, and comparability with other laboratories should be performed if possible.
The first mandatory test is to validate the identity of the iPSC line with the short tandem repeat (STR) analysis to genotype the original cells, the iPSC seeds and the master cell bank to ascertain the absence of switch or cross contamination of several iPSC lines during generation or maintenance process. Due to the nature of the stem cell-based products, they cannot be sterilized. The assessment of the microbiological sterility is of the highest importance and should be performed not only on the final product. This should include the mycoplasma, bacteriology and viral testing supplemented by endotoxins detection assay and should have a negative result. The genetic stability and fidelity of the iPSC lines should be evaluated by residual vector testing and karyotype. To eliminate the risk of potential cell transformation and the risk of malignancy development in patients, residual vector testing has to be ≤1 plasmid copy per 100 cells in seed and master cell banks and the karyotype should be normal on more than 20 metaphases. So far, techniques with high precision such as single nucleotide polymorphism (SNP) and whole genome analysis or other genetic markers are not required but could be performed for information. To give an appropriate dosage of cells, viability should be >60%. Calculation of doubling time and detection of cell debris are not required but could provide useful information. To manage the risk associated with the presence of non-desired or spontaneously differentiated cells, iPSCs have to be characterized by the expression of a minimum of two markers from the standard human pluripotent stem cells panel (positive for Oct4, TRA-1-60, TRA-1-81, SSEA-3, SSEA-4, Sox2, Nanog). A combination of one intracellular and one extracellular marker should be used and should be >70%. Finally, for the potency assay, reflecting the biological activity of the cells, embryoid body formation or directed differentiation of monolayer cultures to produce cell types representative of all three embryonic germ layers is mandatory. The teratoma formation in severe combined immune-deficient (SCiD) mouse injection assay is not mandatory for the iPSC due to a reproducibility problem, high cost and non-ethical procedure. Molecular pluripotency assays such as mRNA array- and RNA-Seq-based gene expression assays could be kept for information if they are performed molecular pluripotency assays such as mRNA array- and RNA-Seq-based gene expression assays could be for information but are not required. For the iPS-derived differentiated therapeutic products, the minimal criteria are mostly identical except for the phenotypical characterization, which should validate the absence of pluripotent stem cell markers, the expression of differentiation markers unique to the therapeutic product and assess 100% purity of the therapeutic cellular product without any contaminating other lineage cell types.
This consensus on CQA and minimum testing requirements for clinical-grade iPSC lines will evolve with the advances in scientific understanding and development in technology and best practices. The Global Alliance for iPSC Therapies (GAiT), which facilitates the development of general clinical-grade iPSC standards by community engagement and consensus building to support the global application of iPSC-derived cellular therapeutics, is in charge of the future evolution of the consensus on quality and safety standards required for a clinical-grade iPSC. Moreover, GAiT presents objectives to achieve consensus on donor selection and screening criteria and consent standards, which with future commercialization and global distribution also require ethical review.
It is quite remarkable that in just over 10 years, research using iPSC has led to several clinical studies, with many more applications expected to follow. In few years, the iPSC-based therapies induced a switch to a mass production of clinical-grade iPSC for the benefit of a large population at affordable costs, with the generation of clinical-grade iPSC banks, and with a stronger involvement of biopharmaceutical companies. This shift led to many efforts for the standardization of generation, maintenance and differentiation procedures, and for the establishment of quality and safety standards for the clinical-grade iPSC and their derivatives prior to transplantation to patients.
There are still a number of challenges that must be overcome for iPSCs to reach their full potential. The improvement of manufacturing procedures for a large-scale production would provide higher quality cells for clinical iPSC-based therapies. Quality and safety controls are also challenging. Predicting cancer risk based on sequence information is a formidable task, and failure to detect oncogenic mutations is not necessarily a warrantor of the non-tumorigenicity of iPSC-based products, suggesting that recommendations should still evolve with scientific advances.
Due to their large potential in regenerative medicine, such as the generation of complex 3D structures, tissues or organs, more challenges in differentiation protocols in 3D structures have to be overcome for the up-coming year, without compromising quality and safety of iPSCs.
The authors declare no conflict of interest.
Authors are listed below with their open access chapters linked via author name:
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\n\n\n\n\n\n\n\n\n\nJocelyn Chanussot (chapter to be published soon...)
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