过表达miR-494和miR-338的hWJ-MSCs移植治疗脊髓损伤及其机制研究

Treatment of spinal cord injury (SCI) is one of the medical mysteries that we have always failed to solve. Among the pathological changes after SCI, destruction of the myelin structure could cause permanent and severe loss of nerve function, thus myelin regeneration is a vital part in the treatment of SCI. The previous research have achieved significant acceleration in myelination formation of regenerating axons after peripheral nerve injury and promoted the functional recovery of extremities. However, the survival, proliferation and differentiation of hWJ-MSCs in the site of SCI is still needed to be further explored. The current research will apply hWJ-MSCs overexpressing miR-494 and miR-338 in the treatment of SCI. By down-regulating apoptosis accelerators such as PTEN and by down-regulating differentiation inhibitors such as Sox6 and Hes5, optimize survival of hWJ-MSCs in the site of spinal cord injury, guide the differentiation of hWJ-MSCs into oligodendrocytes, promote myelin regeneration and functional recovery after SCI. The current research will prove the applicability of hWJ-MSCs overexpressing miR-494 and miR-338 in the treatment of SCI, explore its mechanisms and provide new ideas and techniques for the treatment of SCI.

脊髓损伤（SCI）的治疗是人类一直未能解决的医学难题。SCI后发生的病理变化中髓鞘结构的损伤会导致永久而严重的神经功能丧失，而恢复髓鞘再生是SCI修复的重要环节。在前期研究中,利用人脐带Wharton胶间充质干细胞（hWJ-MSCs）植入以及微小RNA（miR）过表达等技术显著促进了周围神经损伤后再生轴突髓鞘化和功能的恢复, 但hWJ-MSCs在脊髓损伤环境下存活，增殖，分化等问题尚需进一步探索。本研究将利用过表达miR-494和miR-338的hWJ-MSCs移植治疗SCI，通过负调控PTEN等的促凋亡因子和Sox6,Hes5等分化抑制因子，优化hWJ-MSCs在脊髓受损部位的存活，并促进其定向分化成少突胶质细胞,促进髓鞘再生，进而加快SCI修复。本研究将证实过表达miR-494和miR-338的hWJ-MSCs移植治疗SCI的可行性，并阐明其机制，为SCI的治疗提供新思路和新手段。

脊髓损伤的治疗是人类一直未能解决的医学难题。脊髓损伤后发生的病理变化中髓鞘结构的损伤会导致永久而严重的神经功能丧失，而恢复髓鞘再生是脊髓损伤修复的重要环节。本研究在前期研究工作的基础上综合利用过表达微小RNA(miR)-494和miR-338的人Wharton胶脐带间充质干细胞移植治疗大鼠脊髓损伤，利用功能学，电生理学，组织病理学以及免疫组织化学检测等手段判断过表达miR-494和miR-338的人Wharton胶脐带间充质干细胞对脊髓损伤修复的治疗效果，并通过分子生物学实验研究发现miR-494和miR-338可通过负调控PTEN等的促凋亡因子和Sox6,Hes5等分化抑制因子优化人Wharton胶脐带间充质干细胞在脊髓受损部位的存活，并促进其定向分化成少突胶质细胞,促进髓鞘再生，进而加快脊髓损伤的修复。本研究证实了过表达miR-494和miR-338的人Wharton胶脐带间充质干细胞移植治疗脊髓损伤的可行性，并阐明了其作用的机制，为利用经过微小RNA改良的脐带间充质干细胞治疗脊髓损伤提供了实验基础。