Meniscal engraftment of iPSC-derived cartilage particles as hyaline and fibrous cartilage in a rabbit injury model

Meniscal tears are associated with the development of knee osteoarthritis. The meniscus partly consists of avascular hyaline cartilage-like tissue with a low self-healing potential. Consequently, the treatment of meniscal injuries remains challenging. Therefore, we aimed to investigate the efficacy of the transplantation of hyaline cartilaginous particles generated from human induced pluripotent stem cells (hiPSC) for meniscal repair. HiPSCs were cultured under chondrogenic differentiation conditions to generate hyaline cartilaginous particles. The study comprised three groups: the hiPSC-cartilage transplant (hiPSC-Cart), rabbit autogenous cartilage transplant (Rab-Cart), and control groups. In the hiPSC-Cart group, hiPSC-Cart was transplanted into the right knee; the left knee was untreated and served as the control. In the Rab-Cart group, articular cartilage was harvested from the rabbit femoral trochlear groove and transplanted into the meniscal defect. The menisci were collected 4 weeks postoperatively and histologically evaluated using safranin O/fast green staining. Immunohistochemistry for human mitochondria and in situ hybridization with a human ribosomal RNA oligoprobe were performed to detect human-derived cells in the tissues. The defect was filled with safranin O-unstained fibrous tissue in the control group, whereas it was filled with tissue containing cartilage components stained with safranin O in the Rab-Cart group. The transplant area exhibited two distinct repair patterns in the hiPSC-Cart group. Hyaline-rich repair was filled with tissues containing a large hyaline-cartilaginous portion that was positive for Safranin O. In contrast, fibrous-rich repair was filled with safranin O-negative fibrous cartilage. Human mitochondria- and ribosomal RNA-positive cells were detected within the transplanted area in both hyalin-rich and fibrous-rich repairs. Transplanted hiPSC-derived hyaline cartilaginous particles engrafted with the surrounding meniscus to facilitate meniscal repair. These results demonstrate the therapeutic potential of iPSC-derived cartilage particles in meniscal repair and regeneration. • Human induced pluripotent stem cells were transplanted into injured rabbit menisci. • Stem cell-derived cartilaginous particles engrafted into the surrounding meniscus. • The stem cell-derived cartilaginous particles mediated meniscus repair. • Human-derived cells were detected in the meniscus at 4 weeks post-transplantation.