iPSCs复合纳米壳聚糖水凝胶治疗骨性关节炎及其机制研究

Osteoarthritis (OA) is seriously deteriorate the life quality of the elderly and there is no effective drugs clinically available. Currently, induced pluripotent stem cell (iPSCs) is the hotspot in the field of regenerative tissue engineering. However, it remains unclear whether the cartilage cell induced from iPSCs could treat the cartilage damage of OA effectively and safely or not. Chitosan has many advantages (easy acquisition, non-toxic, etc), which provides the optimal biological scaffolds for tissue engineering. Our preliminary data indicated that the iPSCs can be induced into cartilage cells in vitro and we also have developed the nano chitosan which confers the advantages of both chitosan and nanomaterial. Based on our promising finding, we propose firstly to label the iPSCs by the lentivirus with green fluorescent protein (GFP), perform the induction and, identification of the cartilage cells as well as the tumorigenicity study, and then to investigate the cartilage differentiation potential and safety of iPSCs. Secondly, we will investigate the biocompatibility and safety of the injectable thermosensitive nano chitosan-based hydrogel in vivo and vitro. Finally we will systematically study the efficacy, biosafety and mechanism of iPSCs coupled with nano chitosan-based hydrogel by OA animal models. We believe the implementation of this project will demonstrate the therapeutic effect of minimally invasive biological treatment (iPSCs as seed cells and nano chitosan as biological scaffolds) for the cartilage damage of OA. This proposal will pave the way to a safe, effective and cell biological therapy for OA with minimal invasion.

骨性关节炎（OA）严重影响老年人生活质量，目前尚无根治药物。诱导多能干细胞（iPSCs）是目前再生组织工程领域研究热点，但其治疗OA软骨损伤的有效性和安全性尚不确定。壳聚糖是组织工程中优选的生物支架。我们前期研究显示iPSCs能在体外定向诱导为软骨细胞; 制备了兼有壳聚糖及纳米材料双重优点的纳米壳聚糖。本研究拟在前期研究基础上，首先通过携带绿色荧光蛋白（GFP）的慢病毒标记iPSCs，并对其进行软骨细胞诱导、鉴定及致瘤性研究，明确其软骨分化潜能及安全性；其次，制备可注射温敏性纳米壳聚糖水凝胶，并通过体内外实验证明其生物相容性；最后，通过OA小鼠模型，系统研究iPSCs复合纳米壳聚糖水凝胶对OA软骨损伤的治疗作用、安全性及其作用机制，明确以iPSCs为种子细胞、纳米壳聚糖为支架的微创生物治疗对OA软骨损伤的治疗效果及可行性。以期探索出一条安全、有效、微创的OA细胞生物新疗法。

骨性关节炎（OA）严重影响老年人生活质量，目前尚无根治药物。诱导多能干细胞（iPSCs）是目前再生组织工程领域研究热点，但其治疗OA软骨损伤的有效性和安全性尚不确定。本研究首先通过携带绿色荧光蛋白（GFP）的慢病毒标记iPSCs，并对其进行软骨细胞诱导、鉴定及致瘤性研究，明确其可向软骨分化且安全性好；其次，制备可注射温敏性纳米壳聚糖水凝胶，并通过体内外实验证明其生物相容性好；最后，通过OA小鼠模型，研究结果显示iPSCs复合纳米壳聚糖水凝胶对OA软骨损伤的具有较好治疗作用，且安全性好。本研究明确了以iPSCs为种子细胞、纳米壳聚糖为支架的微创生物治疗对OA软骨损伤的治疗效果及可行性，为OA细胞生物新疗法探索了新途径。