Bone and cartilage repair by transplantation of induced pluripotent stem cells in murine joint defect model

Abstract

The establishment of cartilage regenerative medicine has been an important issue in the clinical field, because cartilage has the poor ability of self-repair. Currently, tissue engineering using autologous chondrocytes has risen, but we should investigate more appropriate cell sources that can be obtained without any quantitative limitation. In this study, we focused on induced pluripotent stem (iPS) cells, in which the ethical hurdle does not seem higher than that of embryonic stem cells. Mouse iPS cells were transplanted into the mouse joint defect model of the knee. Strains of the transplants and hosts were arranged to be either closest (homology 75% in genetic background) or identical (100%). For transplantation, we embedded the iPS cells within the collagen hydrogel in order to obtain the effective administration of the cells into defects, which induced the differentiation of the iPS cells. At 8 weeks of transplantation, although the iPS cells with a 75% homology to the host in the genetic background tended to form teratoma, those of 100% showed a joint regeneration. GFP immunohistochemistry proved that the transplanted iPS cells were responsible for the bone and cartilage repair. Taking these results together, the iPS cells are regarded as a promising cell source for the cartilage tissue engineering.

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

“…the risk of tumorigenesis that has been observed in a previous study using mouse iPSCs (13). In the present study, a tumor was found in one mouse at 16 weeks after transplantation, indicating an incidence of 6.7%.…”

“…In addition, iPSCs are free from ethical concerns that are inevitable when using embryonic stem cells (ESCs). Several studies have shown the potential of iPSCs in cartilage regenerative medicine (9,(12)(13)(14). On the other hand, the risk of tumorigenesis should be considered in the clinical application of human iPSCs (hiPSCs) (13).…”

“…Several studies have shown the potential of iPSCs in cartilage regenerative medicine (9,(12)(13)(14). On the other hand, the risk of tumorigenesis should be considered in the clinical application of human iPSCs (hiPSCs) (13). Recently, Oldershaw et al reported a novel method for differentiation from human ESCs (hESCs) toward chondrocytes (7).…”

Cellular and Acellular Approaches for Cartilage Repair

“…Such findings raise concerns about using IPS cells for clinical cartilage repair purposes. 33 Also, Uto et al 34 speculated that perhaps due to insufficient local factors reaching the transplanted IPS cells, there was a risk for an increase in the remaining undifferentiated cells to induce tumor formation. However, they were more optimistic and stated that perhaps IPS cells could be the dominant cell source in bone and cartilage regenerative medicine if cell selection and management were conducted properly and if the mechanical condition was in control after surgery.…”

Cartilage repair techniques in the knee: stem cell therapies

“…Rat and mouse models have been used in some studies [32][33][34][35][36]. In those animal models, in general, rather novel approaches to the stem cell therapy such as magnetically labeled MSC, gene transfer, uses of induced pluripotent stem (iPS) and embryonic stem (ES) cells were examined for their future possibilities.…”