基于SKP-SCs来源胞外囊泡构建的神经移植物桥接周围神经缺损的生物安全性评价

Biosafety evaluation of nerve grafts incorporated with extracellular vesicles from skin-derived precursor Schwann cells for repair of peripheral nerve defects

目的:评价基于皮肤源性前体细胞(skin-derived precursors,SKPs)分化的施万细胞(Schwann cells,SCs)来源的胞外囊泡(extracellular vesicles,EVs)构建的神经移植物用于修复周围神经缺损的生物安全性。方法:构建大鼠坐骨神经离断模型,将基质胶装载的SKP-SC-EVs注射至硅胶管制备含囊泡神经移植物(EV-NG),修复坐骨神经损伤。观察术后大鼠运动状态,12周后收集血液进行血常规和生化指标分析,取心、肝、脾、肺、肾、脑组织切片通过HE染色进行病理组织学分析。结果:病理检查显示各组大鼠各重要脏器组织结构清晰,血常规和生化指标均在正常参考范围内,与假手术组比较,EV-NG组与假手术组的差异均无统计学意义(P>0.05)。结论:装载SKP-SC-EVs的神经移植物具有良好的生物安全性,为临床治疗周围神经缺损提供安全性依据。

Objective:This study aims to evaluate the biosafety of nerve grafts constructed from extracellular vesicles derived from skin precursor-derived Schwann cells(SKP-SC-EVs)for repairing peripheral nerve defects.Methods:The rat sciatic nerve transection model was established.The Matrigel loaded with SKP-SC-EVs was injected into a silicone tube to prepare a nerve graft(EV-NG)for repairing the sciatic nerve injury.After the operation,the state of the rats was observed.After 12 weeks,The blood was collected for blood routine and biochemical analysis.The hearts,livers,spleens,lungs,kidneys,and brains were taken for pathological analysis by HE staining.Results:Morphological analysis showed that the tissue structure of each organ was clear,and no toxic reaction symptoms were observed in rats of each group;the blood indexes of each group were within the normal reference range.Compared with the sham operation group,the blood indexes of the EV-NG group had no significant difference(P>0.05).Conclusion:The nerve graft incorporated with SKP-SC-EVs has good biosafety,which provides safety data support for treating the clinical repair of peripheral nerve injury.