Pluripotent Stem Cells: Embryonic/ Fetal Stem Cells and Induced Pluripotent Stem Cells

Abstract

Musculoskeletal regenerative medicine encompasses strategies for the regeneration of bone, cartilage, tendon, ligament, muscle, fat, and other connective tissues. Perhaps the greatest unmet need is cartilage preservation, repair, and regeneration. Most of the reported approaches in regenerative medicine for chondral defects and osteoarthritis (OA) have been based on adult stem cells, but pluripotent stem cells also merit a consideration as potential cell sources with their advantage in plasticity and unlimited expansion potential. While embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are similar to each other in almost all cellular characteristics, iPSCs are preferred to ESCs because iPSCs do not have religious and ethical issues and autogenous iPSCs are free from the risk of immune rejection unlike ESCs. While iPSCs were first induced using either retrovirus or lentivirus, non-integrating vectors are currently preferred for the generation of iPSCs. Several methods to differentiate ESCs/iPSCs toward chondrocytes have been developed. iPSCs may become a useful cell source for regenerative therapies for chondral defects and OA, provided that safe and reliable ways of producing iPSC-derived chondrocytes are established. One of the unique characteristics seen from in vitro chondrogenic differentiation of iPSCs is the low expression of hypertrophic markers. This may indicate that iPSC-derived chondrocytes have a more stable phenotype, unlike mesenchymal stromal cells (MSCs). Also, in vivo studies on iPSC treatment to joints of small animals demonstrated enhanced survival and engraftment of implanted cells after several months. This may increase the chance of articular cartilage regeneration and durable matrix synthesis, rather than primarily paracrine effects on endogenous cells. Further investigations in larger animal models are necessary for a more accurate assessment of the efficacy and safety of in vivo implantation of iPSCs. © ISAKOS 2022.