Chapters authored
Cartilage Regeneration Using Pluripotent Stem Cell‐Derived Chondroprogenitors: Promise and Challenges
The cartilage of joints is long‐lasting (i.e., permanent) cartilage and is not spontaneously repaired after injury in humans. There has been considerable interest in the clinical application of stem cells to the repair of damaged cartilage; however, current cell therapies using adult chondrocytes and mesenchymal stromal cells face problems associated with the low yield of such cells. The expansion culture, needed before transplantation, leads to the formation of fibrocartilage or growth plate-like (i.e., bone‐forming) cartilage in vivo. Both types of cartilage are unsuitable for the repair of joint cartilage such as meniscus and articular cartilage. Joints are formed during embryogenesis. Therefore, we hypothesize that embryonic progenitor cells responsible for the development of joint cartilage would be the best for regenerating joint cartilage in the adult. Pluripotent stem cells (PSCs) are expected to differentiate in culture into any somatic cell types through processes that mimic embryogenesis, making human (h)PSCs a promising source of embryonic cells for regenerative medicine. However, regardless of the cell system used, the major research goals leading to clinical application to cartilage regeneration are to (1) expand chondrogenic cells (chondroprogenitors) to sufficient numbers without loss of their chondrogenic activity, and (2) direct the differentiation of such cells in vivo or in vitro toward articular or other types of chondrocytes of interest. The overall aim of the current review was to provide the basis of a strategy for meeting the goals for cartilage regeneration by the use of hPSC‐derived chondroprogenitor cells. We provide an overview on signaling mechanisms that are known to affect the expandability and chondrogenic activity of adult and embryonic chondroprogenitors, as well as their differentiation in vivo or in vitro toward a particular type of chondrocyte. We then discuss alternative types of progenitor cells that might replace or combine with the hPSC‐derived chondroprogenitors to regenerate permanent cartilage. We also include our recent achievement of successfully expanding hPSC‐derived neural crest to generate ectomesenchymal chondroprogenitors that can be maintained for a long term in culture without loss of chondrogenic activity. Finally, we provide information on the challenges that hPSC progeny‐based regenerative medicine will face, and discuss the implications for such challenges for the future use of PSC progeny to regenerate cartilage.
Part of the book: Pluripotent Stem Cells