PDF(Pubmed)
Abstract：
Peripheral nerve injury (PNI) is a relatively frequent type of trauma that results in the suffering of many patients worldwide every year. Schwann cells (SCs) are expected to be applied in cell therapy because of their ability to promote peripheral nerve regeneration. However, the lack of clinically renewable sources of SCs hinders the application of SC-based therapies. Adipose-derived stem cells (ADSCs) have generated great interest in recent years because of their multipotency and ease of harvest, and they have already been verified to differentiate into Schwann-like cells (SLCs) in vitro. However, the efficiency of differentiation and the functions of SLCs remain unsatisfactory. We newly generated three-dimensional (3D) SLC spheroids from ADSCs using a modified protocol with human recombinant peptide (RCP) petaloid μ-piece. Morphological analysis, gene expression analysis by qRT-PCR, ELISA measurement of the secretion capabilities of neurotrophic factors, and neurite formation assay were performed to evaluate the functions of these 3D SLCs in vitro. Motor function recovery was measured in a sciatic nerve injury mouse model to analyze the nerve regeneration-promoting effect of 3D SLCs in vivo. The differentiation efficiency and the secretion of neurotrophic factors were enhanced in 3D SLCs compared with conventional SLCs. 3D SLCs could more effectively promote neurite growth and longer neurite extension in a neuron-like SH-SY5Y model. Additionally, 3D SLCs had a better therapeutic effect on nerve regeneration after transplantation into the sciatic nerve injury mouse model. These findings demonstrated that the potential of ADSC-derived SLCs to promote nerve regeneration could be significantly increased using our modified differentiation protocol and by assembling cells into a 3D sphere conformation. Therefore, these cells have great potential and can be used in the clinical treatment of PNI.
摘要：
周围神经损伤（PNI）是一种相对常见的创伤类型，每年导致全球许多患者遭受痛苦。雪旺氏细胞(SCs)因其促进外周神经再生的能力而有望应用于细胞治疗。然而,缺乏临床上可再生资源的SCs阻碍了基于SC的疗法的应用.脂肪来源的干细胞（ADSC）由于其多能性和易于收获，近年来引起了极大的兴趣，它们已经被证实在体外分化成雪旺样细胞(SLC)。然而,SLC的分化效率和功能仍然不尽人意。我们使用人重组肽（RCP）花瓣状μ片的改良方案，从ADSC新生成了三维（3D）SLC球体。形态学分析,通过qRT-PCR分析基因表达，ELISA测量神经营养因子的分泌能力，和神经突形成测定进行体外评估这些3DSLCs的功能。在坐骨神经损伤小鼠模型中测量运动功能恢复以分析3DSLCs在体内的神经再生促进作用。与常规SLCs相比，3DSLCs的分化效率和神经营养因子的分泌增强。在神经元样SH-SY5Y模型中，3DSLCs可以更有效地促进神经突生长和更长的神经突延伸。此外,3DSLCs对坐骨神经损伤小鼠模型移植后的神经再生有较好的治疗作用。这些发现表明，使用我们修改的分化方案并通过将细胞组装成3D球体构象，可以显着增加ADSC衍生的SLC促进神经再生的潜力。因此,这些细胞具有很大的潜力,可用于PNI的临床治疗。
