Generation of scaffoldless hyaline cartilaginous tissue from human iPSCs.
Bottom Line: Defects in articular cartilage ultimately result in loss of joint function.The immunodeficiency mice and rats suffered from neither tumors nor ectopic tissue formation.The hiPSC-derived cartilaginous particles constitute a viable cell source for regenerating cartilage defects.
Affiliation: Cell Induction and Regulation Field, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.Show MeSH
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Mentions: We transplanted hiPSC-derived cartilaginous particles into defects created in the articular cartilage of SCID rats. Due to the small size and limited depth of the rat cartilage, we were unable to fix mature particles that were lubricious in their defects. Therefore, we transplanted premature-hiPSC-derived cartilaginous particles obtained on day 28. The defects were filled with hiPSC-derived cells in three of four knees at 1 week and three of four knees at 4 weeks after transplantation, as indicated by the expression of human vimentin (Figure 6A). The day-28 particles produced tissue that exhibited metachromatic staining with toluidine blue and a strong expression of type II collagen in the articular cartilage defects (Figures 6A and 6B), which differs from the observation that day-28 particles fail to produce mature cartilage in subcutaneous spaces. We speculate that the orthotopic environment might stimulate the maturation of day-28 particles. Side-to-side integration between the tissues formed by the transplanted cells and the rat articular cartilage was strongly achieved (Figure 6B). There were no signs of teratomas or other tumors in any of the four transplanted sites.
Affiliation: Cell Induction and Regulation Field, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.