주지현 (가톨릭대학교) | 한빛사논문 > 한빛사

한빛사논문

조회471

가톨릭대학교

CV File 266 kb

Acta Biomater., 2023 Jun 7;S1742-7061(23)00317-3 | https://doi.org/10.1016/j.actbio.2023.05.052 Prochondrogenic effect of decellularized extracellular matrix secreted from human induced pluripotent stem cell-derived chondrocytes

Si Hwa Choi ^a,b, Kijun Lee ^c, Heeju Han ^a,b, Hyunkyung Mo ^a,b, Hyerin Jung ^c, YoungWoo Ryu ^a,b, Yoojun Nam ^c, Yeri Alice Rim ^b, Ji Hyeon Ju^a,b,c,d

^aCatholic iPSC Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
^bDepartment of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea
^cYiPSCELL, Inc., Seoul, South Korea
^dDivision of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

Corresponding authors: Yeri Alice Rim, Ji Hyeon Ju

Abstract

Cartilage is mainly composed of chondrocytes and the extracellular matrix (ECM), which exchange 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 the 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 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 suggested the prochondrogenic effect of hiPSC-derived cartilage-like dECM and offered a promising approach as a non-cellular 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.

논문정보

형식Research article
게재일2023년 06월 (BRIC 등록일 2023-06-23)
연구진국내 연구진
분야 생명과학 > 생물공학

댓글 작성 로그인

CV 열람하기

연락처 보기