Recent progress of animal transplantation studies for treating articular cartilage damage using pluripotent stem cells

Abstract

Focal articular cartilage damage can eventually lead to the onset of osteoarthritis with degradation around healthy articular cartilage. Currently, there are no drugs available that effectively repair articular cartilage damage. Several surgical techniques exist and are expected to prevent progression to osteoarthritis, but they do not offer a long‐term clinical solution. Recently, regenerative medicine approaches using human pluripotent stem cells (PSCs) have gained attention as new cell sources for therapeutic products. To translate PSCs to clinical application, appropriate cultures that produce large amounts of chondrocytes and hyaline cartilage are needed. So too are assays for the safety and efficacy of the cellular materials in preclinical studies including animal transplantation models. To confirm safety and efficacy, transplantation into the subcutaneous space and articular cartilage defects have been performed in animal models. All but one study we reviewed that transplanted PSC‐derived cellular products into articular cartilage defects found safe and effective recovery. However, for most of those studies, the quality of the PSCs was not verified, and the evaluations were done with small animals over short observation periods. Large animals and longer observation times are preferred. We will discuss the recent progress and future direction of the animal transplantation studies for the treatment of focal articular cartilage damages using PSCs.

Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect

“…Induced pluripotent stem (iPS) cells are a promising source for the regenerative treatment of articular cartilage damage 10 , 11 . Cartilage consisting of chondrocytes and ECM has been successfully created from iPS cells by differentiating them into chondrocytes, which are subsequently transferred into a three-dimensional culture to make iPS cell-derived chondrocytes produce and accumulate ECM around themselves to form cartilaginous tissue particles 12 , 13 .…”

Challenges Facing the Translation of Embryonic Stem Cell Therapy for the Treatment of Cartilage Lesions

“…Several small animal models have demonstrated in vivo evidence of cartilage regeneration using hESC. 31 , 32 , 37 , 55 , 56 , 76 , 77 However, animal studies have not progressed to clinical trials, suggesting a need to revisit the true value of these models. It is essential to establish a validated translational pipeline that progresses reliably from in vitro, ex vivo, and small animal proof of concept to definitive preclinical studies in large animals.…”

Differences in the intrinsic chondrogenic potential of human mesenchymal stromal cells and iPSC‐derived multipotent cells

“…In recent years, many researchers have tested iPSCs as a new cell source for regenerating articular cartilage. 7 , 31 , 32 , 33 , 34 , 35 , 36 In this study, we side‐by‐side compared the quality of cartilage derived from hMSCs and iMPCs and examined their reparative capacity in a rodent animal model. In addition, we conducted a mechanistic study to understand why MSCs and iMPCs respond differently to chondro‐induction factors.…”

“…Concomitant chondrocytic hypertrophy, a phenotype that is not seen in healthy hyaline cartilage, is often accompanied with MSC chondrogenesis. In recent years, many researchers have tested iPSCs as a new cell source for regenerating articular cartilage 7,31–36 . In this study, we side‐by‐side compared the quality of cartilage derived from hMSCs and iMPCs and examined their reparative capacity in a rodent animal model.…”