<b>Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem </b><b>cells </b>

Abstract

Induced pluripotent stem cells (iPSCs) are a promising cell source for cartilage regenerative medicine. Meanwhile, the risk of tumorigenesis should be considered in the clinical application of human iPSCs (hiPSCs). Here, we report in vitro chondrogenic differentiation of hiPSCs and maturation of the differentiated hiPSCs through transplantation into mouse knee joints. Three hiPSC clones showed efficient chondrogenic differentiation using an established protocol for human embryonic stem cells. The differentiated hiPSCs formed hyaline cartilage tissues at 8 weeks after transplantation into the articular cartilage of NOD/SCID mouse knee joints. Although tumors were not observed during the 8 weeks after transplantation, an immature teratoma had developed in one mouse at 16 weeks. In conclusion, hiPSCs are a potent cell source for regeneration of hyaline articular cartilage. However, the risk of tumorigenesis should be managed for clinical application in the future.

Characterization of Mesenchymal Stem Cell-Like Cells Derived From Human iPSCs via Neural Crest Development and Their Application for Osteochondral Repair

“…However, such protocols require multiple serial procedures involving several different mediums and coating vessels. Due to the lack of a purification step, the risks for contamination by tumorigenic pluripotent cells [73, 85] and heterogenity with regard to the presence of cells of different lineage cells are a concern with such protocols. On the other hand, in mesodermal development, paraxial mesoderms, which are sorted by PDGFRa (+) /KDR (−) cells from PSCs [22, 86–90], could be promising progeny to generate hyaline cartilage.…”

Comparison of Four Protocols to Generate Chondrocyte-Like Cells from Human Induced Pluripotent Stem Cells (hiPSCs)

“…Regardless of the technique used to obtain chondrocytes from hiPSCs, the available evidence [22, 23] suggests that there may be a risk of tumorigenesis. Although implanted chondrocytes derived from hiPSCs can successfully regenerate cartilage tissue, they may also lead to tumor formation due to the development of immature teratomas from residual, undifferentiated hiPSCs; in addition, there is a risk of developing differentiated tumors, such as chondrosarcomas, originating from hiPSC-derived chondrocytes with genomic abnormalities [22, 23].…”

“…Although implanted chondrocytes derived from hiPSCs can successfully regenerate cartilage tissue, they may also lead to tumor formation due to the development of immature teratomas from residual, undifferentiated hiPSCs; in addition, there is a risk of developing differentiated tumors, such as chondrosarcomas, originating from hiPSC-derived chondrocytes with genomic abnormalities [22, 23]. Chondrocytes derived from hiPSCs are therefore not without risk and more research into the genetic stability of these chondrocyte-like cells is needed.…”

Perspectivas de terapia celular em neurologia

“…A ocorrência de teratomas é um risco evidenciado por uma série de estudos [63][64][65] ; faz-se necessário compreender melhor os riscos tumorigênicos antes de partirmos para ensaios clínicos e testes em humanos. Basicamente, o aumento do potencial de diferenciação celular está diretamente relacionado a um maior potencial replicativo, o que por sua vez favorece a degeneração maligna.…”