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Updated: Jul 27, 2025
Synthesis of Decellularized Cartilage Extracellular Matrix Hydrogels
Published on: July 21, 2023
Prochondrogenic effect of decellularized extracellular matrix secreted from human induced pluripotent stem
Si Hwa Choi1, Kijun Lee2, Heeju Han1
1Catholic iPSC Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea.
Abstract:
Cartilage is mainly composed of chondrocytes and the extracellular matrix (ECM), which transmits important biochemical and biomechanical signals necessary for differentiation and homeostasis. Human articular cartilage has a low ability for regeneration because it lacks blood vessels, nerves, and lymphatic vessels. Currently, cell therapeutics, including stem cells, provide a promising strategy for cartilage regeneration and treatment; however, there are various hurdles to overcome, such as immune rejection and teratoma formation. In this study, we assessed the applicability of stem cell-derived chondrocyte ECM for cartilage regeneration. Human induced pluripotent stem cell (hiPSC)-derived chondrocytes (iChondrocytes) were differentiated, and decellularized ECM (dECM) was successfully isolated from cultured chondrocytes. Isolated dECM enhanced the in vitro chondrogenesis of iPSCs when recellularized. Implanted dECM also restored osteochondral defects in a rat osteoarthritis model. A possible association with the glycogen synthase kinase-3 beta (GSK3β) pathway demonstrated the fate-determining importance of dECM in regulating cell differentiation. Collectively, we suggest the prochondrogenic effect of hiPSC-derived cartilage-like dECM and offer a promising approach of a noncellular therapeutic for articular cartilage reconstruction without cell transplantation. STATEMENT OF SIGNIFICANCE: Human articular cartilage has low ability for regeneration and cell culture-based therapeutics could aid cartilage regeneration. Yet, the applicability of human induced pluripotent stem cell-derived chondrocyte (iChondrocyte) extracellular matrix (ECM) has not been elucidated. Therefore, we first differentiated iChondrocytes and isolated the secreted ECM by decellularization. Recellularization was performed to confirm the pro-chondrogenic effect of the decellularized ECM (dECM). In addition, we confirmed the possibility of cartilage repair by transplanting the dECM into the cartilage defect in osteochondral defect rat knee joint. We believe that our proof-of-concept study will serve as a basis for investigating the potential of dECM obtained from iPSC-derived differentiated cells as a non-cellular resource for tissue regeneration and other future applications.
