Repair potential of nonsurgically delivered induced pluripotent stem cell-derived chondrocytes in a rat osteochondral defect model

Abstract

Human induced pluripotent stem cells (hiPSCs) are thought to be an alternative cell source for future regenerative medicine. hiPSCs may allow unlimited production of cell types that have low turnover rates and are difficult to obtain such as autologous chondrocytes. In this study, we generated hiPSC-derived chondrogenic pellets, and chondrocytes were isolated. To confirm the curative effects, chondrogenic pellets and isolated chondrocytes were transplanted into rat joints with osteochondral defects. Isolated hiPSC-derived chondrocytes were delivered in the defect by a single intra-articular injection. The generated hiPSC-derived chondrogenic pellets had increased chondrogenic marker expression and accumulated extracellular matrix proteins. Chondrocytes were successfully isolated from the pellets. Alcian blue staining and collagen type II were detected in the cells. Chondrogenic marker expression was also increased in the isolated cells. Transplanted chondrogenic pellets and chondrocytes both had curative effects in the osteochondral defect rat model. Detection of human proteins in the joints proved that the cells were successfully delivered into the defect. Chondrogenic pellets or chondrocytes generated from hiPSCs have potential as regenerative medicine for cartilage recovery or regeneration. Chondrocytes isolated from hiPSC-derived chondrogenic pellets had curative effects in damaged cartilage. Injectable hiPSC-derived chondrocytes show the possibility of noninvasive delivery of regenerative medicine for cartilage recovery.

Bushenhuoxue Formula Facilitates Articular Cartilage Repair and Attenuates Matrix Degradation by Activation of TGF‐β Signaling Pathway

“…Repairing of articular cartilage lesion remains a challenging issue because of its avascular and aneural nature [ 26 ]. All reparative approaches were trying but failed to achieve the ultimate goal of regeneration and restoration of the hyaline cartilage in the defected area [ 27 ]. Cartilage-to-cartilage integration is extremely difficult to achieve because cartilage displays low metabolism and contains dense, antiadhesive ECM [ 28 ].…”

iPSCs in Modeling and Therapy of Osteoarthritis

“…Despite the successful cartilage formation from iPSC-derived teratoma tissue, this method is not suitable for replacement therapies for OA patients due to transplant animal growth as well as the time-and cost-consuming differentiation process [23]. Recently, the research group of Rim et al [24] proved the therapeutic effect of iPSC-derived chondrocytes delivered only by single intra-articular injection into the rat model with the osteochondral defect. Eight weeks post-transplantation, the high recovery capacity of injected iPSC-derived chondrocytes, which formed lacunae in vivo, were detected.…”

“…A short time ago, it was found that the paracrine factors such as Ihh and Runx also influence chondrogenic differentiation of iPSCs [28][29][30]. There are currently four main chondrogenic differentiation approaches including (a) the generation of MSC-like iPSCs and their subsequent differentiation into chondrocytes [31,32]; (b) the co-culture of iPSCs-derived MSCs with primary chondrocytes [33]; (c) through the formation of embryoid bodies (EBs) [19,24,34,35]; and (d) culturing of iPSCs in a series of media architected to mimic normal developmental pathways [20,22]. iPSC formation through EBs together with their subsequent co-cultivation with chondrocytes was performed by Wei et al [35].…”

Characterization of Early-Onset Finger Osteoarthritis-Like Condition Using Patient-Derived Induced Pluripotent Stem Cells

“…Chondrogenic differentiation was conducted using our previous methods [5,[9][10][11][12]. A 1:1 mixture of E8 media (Thermo Fisher Scientific) and Aggrewell media (StemCell Technologies, Vancouver, BC, Canada) was added to hiPSCs (1-5 × 10 4 cells per cm 2 ) for embryonic body (EB) formation, which were maintained in a petri dish with E8 media and 10 µM rho-associated kinase (ROCK) inhibitor (ROCKi) for 24 h. The formed EB clusters were then maintained in E8 media without ROCKi for an additional 48 h.…”