iPS-MSC来源Exosome促进软骨组织再生修复的分子机理

关节软骨损伤的治疗一直是困扰临床的难题。最新研究表明干细胞移植可有效修复软骨损伤，且干细胞分泌的外泌体（Exosome）具有类似干细胞样的功能，从而为软骨损伤的治疗研究带来新的契机。我们的前期研究发现iPS-MSC分泌的Exosome（iPS-MSC-Exos）可被软骨细胞摄取并显著促进损伤软骨的修复，芯片检测显示iPS-MSC-Exos中含有多种与软骨再生相关miRNAs。结合miRNAs在软骨损伤修复中发挥重要作用的相关报道，我们推测iPS-MSC-Exos可能是通过其携带的某些特异miRNAs调控下游靶基因促进软骨的再生与修复。据此，本课题拟通过系列实验客观评估iPS-MSC-Exos促进软骨再生的功能，明确iPS-MSC-Exos中促进软骨再生的关键miRNAs及其分子途径，阐明iPS-MSC-Exos促进软骨再生的分子机理，为利用干细胞技术治疗软骨损伤性疾病研发新技术提供依据。

Until now treatment of articular cartilage injury has remain plagued clinical challenge. The latest research revealed that stem cell transplantation could effectively promote cartilage regeneration. Moreover, exosomes secreted by stem cells were reported to show similar biological function as stem cell transplantation, which brings new opportunity for the treatment of cartilage injury. Our previous studies showed that exosomes derived from iPS-MSCs (iPS-MSC-Exos) could be absorbed by chondrocytes and significantly promote cartilage tissue repair. Gene chip analysis showed that iPS-MSC-Exos contained a variety of microRNAs which is closely related to articular cartilage injury. Combined with recent reports that microRNAs play important role in cartilage regeneration and tissue repair, we speculate that iPS-MSC-Exos can promote cartilage regeneration through carrying specific miRNAs to regulate downstream target genes. Accordingly, our project plans to evaluate the cartilage repairing effects of iPS-MSC-Exos through series of experiments, and identify key microRNAs and related molecular pathway resposibe for the biological function. Based on the research, we are going to give an preliminary explantation for the molecular mechanism that iPS-MSC-Exos promote cartilage regeneration. This will provide scientific theoretical foundation to utilize stem cell for research and development of new technology for the clinical treatment of osteoarthritis and other cartilage injuries.