Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis

• Published in: Stem cell research & therapy 2017-03, Vol.8 (1), p.64-64, Article 64
• Main Authors: Zhu, Yu, Wang, Yuchen, Zhao, Bizeng, Niu, Xin, Hu, Bin, Li, Qing, Zhang, Juntao, Ding, Jian, Chen, Yunfeng, Wang, Yang
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Age; AKT protein; Animals; Anterior cruciate ligament; Antigens; Arthritis; Autografts; Bone growth; Cartilage diseases; Cell Differentiation - genetics; Cell Proliferation - genetics; Chondrocytes; Chondrocytes - transplantation; Donors; Embryo cells; Exosomes - genetics; Glucose; Graft rejection; Humans; Immunoglobulins; Immunosuppression; Induced Pluripotent Stem Cells; Joint diseases; Limbs; Medical research; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mice; Monoclonal antibodies; Morphology; Neural stem cells; Osteoarthritis - genetics; Osteoarthritis - pathology; Osteoarthritis - therapy; Pluripotency; Recovery of function; Sports injuries; Stem cells; Studies; Surgery; Synovial Membrane - cytology; Synovial Membrane - transplantation; Transplants & implants; Urine
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-017-0510-9

Osteoarthritis (OA) is the most common joint disease worldwide. In the past decade, mesenchymal stem cells (MSCs) have been used widely for the treatment of OA. A potential mechanism of MSC-based therapies has been attributed to the paracrine secretion of trophic factors, in which exosomes may play a major role. In this study, we aimed to compare the effectiveness of exosomes secreted by synovial membrane MSCs (SMMSC-Exos) and exosomes secreted by induced pluripotent stem cell-derived MSCs (iMSC-Exos) on the treatment of OA. Induced pluripotent stem cell-derived MSCs and synovial membrane MSCs were characterized by flow cytometry. iMSC-Exos and SMMSC-Exos were isolated using an ultrafiltration method. Tunable resistive pulse-sensing analysis, transmission electron microscopy, and western blots were used to identify exosomes. iMSC-Exos and SMMSC-Exos were injected intra-articularly in a mouse model of collagenase-induced OA and the efficacy of exosome injections was assessed by macroscopic, histological, and immunohistochemistry analysis. We also evaluated the effects of iMSC-Exos and SMMSC-Exos on proliferation and migration of human chondrocytes by cell-counting and scratch assays, respectively. The majority of iMSC-Exos and SMMSC-Exos were approximately 50-150 nm in diameter and expressed CD9, CD63, and TSG101. The injection of iMSC-Exos and SMMSC-Exos both attenuated OA in the mouse OA model, but iMSC-Exos had a superior therapeutic effect compared with SMMSC-Exos. Similarly, chondrocyte migration and proliferation were stimulated by both iMSC-Exos and SMMSC-Exos, with iMSC-Exos exerting a stronger effect. The present study demonstrated that iMSC-Exos have a greater therapeutic effect on OA than SMMSC-Exos. Because autologous iMSCs are theoretically inexhaustible, iMSC-Exos may represent a novel therapeutic approach for the treatment of OA.