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Introductory Chapter: Organoid Technology and Potential Applications

Written By

Manash K. Paul

Published: 28 September 2022

DOI: 10.5772/intechopen.104249

From the Edited Volume

Organoid Bioengineering - Advances, Applications and Challenges

Edited by Manash K. Paul

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1. Introduction

Owing to the fantastic potential of pluripotent stem cells (PSCs) to develop into all cell types in the body, regulating the differentiation of PSCs into particular tissue types is a substantial challenge. Early attempts to differentiate human PSCs (hPSCs) used two-dimensional (2D) monolayer cultures, resulting in cells that showed germ layer markers but lacked tissue architecture [1, 2]. Because of the potential to generate differentiated cells for therapeutic applications, human-induced pluripotent stem cells (iPSCs) are being researched more and more in stem cell research [3, 4]. Recent research has concentrated on developing organoids from human iPSCs and avoiding the ethical problems connected with embryonic stem cell (ESC) usage. Initial attempts at three-dimensional (3D) structure generation relied heavily on aggregation and spontaneous differentiation, resulting in disorganized tissue mixes [4, 5]. Recently, incredible progress has been made in the in vitro development of 3D organized tissues—dubbed organoids. Organoid technology is a multidisciplinary technique that uses stem cells’ ability to self-renew, differentiate into many lineages, and self-organize into organoids. Scientists have explored human PSCs and adult stem cells (ASCs) to create tiny tissue mimics that resemble a wide variety of organs [6]. Several research groups have now manipulated PSCs and ASCs in vitro to generate endodermal, mesodermal, and ectodermal cell-derived organoids. Organoid culture has been used to promote the development of various tissues, including the kidney, brain, lung, colon, stomach, breast, liver, etc. (Figure 1).

Figure 1.

Human organoids are vital in the progress of human biology research, preclinical investigations, and their translation into successful therapeutics.

Organoid technology has the potential to produce organ-specific tissue organoids and can provide an unprecedented opportunity for effective modeling of human-specific disease and to simulate the physiology and complexity of tissue-specific ailments. Given the existing difference between animal models and human disease pathology, a paradigm shift was needed to model human diseases appropriately. The 3D human organoid platform can aid in acquiring a better knowledge of the pathobiology of human diseases [7]. Organoids throw light on human disease-associated signaling interactions, cell-cell communications, therapeutic target identification, therapeutic discovery, and screening, thereby decoding the process of disease development in humans. Organoids closely replicates human physiology and simulates disorders affecting many organ systems is a more viable alternative to in vivo animal models when studying regenerative medicine [8]. It has now become feasible to use a person’s own stem cells for personalized disease models and precision treatment as a result of improvements in biobanking [9, 10]. This collection of chapters attempts to bring together professionals from a variety of fields in order to shed light on the use of organoids in human disease management.

Organoid-based disease modeling is a rapidly evolving field with significant potential for integrating novel techniques into future investigations [6]. Recent breakthroughs in organoid technology, such as creating a unique organoid platform, the engineering of organoid complexity, and the incorporation of pathological characteristics, have accelerated the development of tiny tissue or organs on a dish. Novel technologies, such as high-resolution 3D imaging, organ on a chip, 3D printing, gene manipulation, and single-cell sequencing, have accelerated the development of organoids, which can provide unprecedented insight into the behavior of stem cells, as well as serve as a platform for preclinical research and theranostics [11, 12]. Genome editing, hybrid culture techniques, biobank development, and single-cell sequencing are all examples of cutting-edge technologies that may help generate more physiologically realistic human disease models, thereby altering the identification of new therapies. A combination of these approaches has the potential to push the frontiers of present scientific study, and future advances will almost certainly result in the development of new paradigms for battling human diseases [7, 12]. This book presents a comprehensive overview of organoids and has three sections: Organ-specific organoid, Patient-derived organoid and tumoroid, and Organoid commercialization.


2. Organ-specific organoid

This section reviews how scientists are cultivating organ-specific tissue from stem cells, which has the potential to revolutionize the way diseases are investigated and treated. Retinal organoids (ROs) are unique to several exciting organoid types. ROs are 3D tissue constructs made from ESCs or iPSCs and accurately reproduce the spatiotemporal differentiation of the retina, making them useful in vitro models of retinal development and retinal disease [13]. ROs, available since 2011, allowed researchers to study retinal development (especially light-sensitive photoreceptors), pathology, and regeneration. The ROs’ differentiation efficiency and development degree have improved dramatically during the last decade and offer many applications, including disease modeling. This section also reviews the role of ROs in evaluating disease pathogenesis, medication screening, and retinal regeneration treatment [14]. Although ROs have a promising future, their lack of structure and function, differentiation and culture constraints, and embryonic retina differences remain unsolved. Neural organoids, or cerebral organoids, are 3D in vitro culture systems produced from hPSCs that mimic the human brain’s development. Specific distinctions between animal and human neurodevelopment have led to a dearth of information about human neurogenesis and understanding the pathological aspect. This section describes the applications of neural organoids in neurodevelopment and regenerative medicine. Advances in stem cell technology and the advent of the human-specific 3D neural organoid model are now widely used to study a specific aspect of the human brain and neurodevelopment. They can be vital in developing more effective therapeutics and regenerative medicine applications [15]. This section reviews current developments and future directions in the brain and retinal organoid developments and their applications.


3. Patient-derived organoid and tumoroid

The current paradigm for preclinical cancer drug development entails extensive and expensive optimization for lead discovery, often using in vitro human-cancer-cell-based models or in vivo animal-based tumor models that do not closely mirror actual solid tumors and, therefore, with little translational value [16]. Multicellular cancer “oids,” including tumoroids, spheroids, and organoids, can address the existing loopholes in conventional 2D human cancer cell cultures and in vivo animal-based cancer models. Cancer “oids” display physiologically relevant cell-cell and cell-matrix interactions, gene expression and signaling pathway profiles, heterogeneity, and structural complexity, all of which are the characteristics of in vivo malignancies [17]. When cultivated appropriately, tumoroids develop easily and exhibit the in vitro model system’s efficacy, repeatability, and resilience. Preclinical researchers are using tumoroids to present case studies on basic tumor biology, host-tumor interactions, and the application of high-throughput screening platforms for anticancer drug discovery and development [18]. This section discusses the evolution of organoids and research trends in cancer research.

This section also reviews patient-derived organoids (PDOs) as a revolutionary model system for cancer research. To circumvent the limitations of established cell lines, PDOs have recently been produced from varied tumor types [18, 19]. Researchers standardized 3D organoid culture methods to expand epithelial stem cells further and differentiate them into genetically and phenotypically stable “mini-organs in a dish,” not only for humans but also for other species [17]. The in vitro response of PDOs mimics that of the result of related patients [20]. PDOs might be used to test immunomodulatory drugs in co-culture with different immune cell types. This book also addresses significant organoid-based bench-to-bedside applications and provides an overview of the therapeutic areas where organoids transform drug discovery and development.


4. Organoid commercialization

Organoids are 3D microtissue replicators that have been successfully employed for various applications, including disease modeling, drug screening, pathogenesis research, stem cell research, and tumor immunology. Organoids are as diverse as the tissues and organs of the human body and have immense economic potential [21, 22]. They have the potential to pave the path for personalized treatment and precision medicine (Figure 1). PDOs have been utilized in clinical trials to predict patient responses to therapy regimens and perhaps enhance cancer treatment results. Recent advances in stem cell research and genomic technology have resulted in ground-breaking breakthroughs in organoid bioengineering, large-scale production, biobanking, and commercialization [6]. This section of the book reviews the concept of organoid biobanking, the firms engaged, the commercialization process, and ethical issues. Additionally, this book discusses possible barriers to clinical translation of organoids and suggests future research avenues for therapeutic translation and cancer treatment. This collection of chapters is intended for a wide readership and will serve as an indispensable resource for fundamental biologists, translational scientists, and clinicians.


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Written By

Manash K. Paul

Published: 28 September 2022