Elucidation of peripheral nerve regeneration-promoting mechanism and in vivo kinetics of transplanted adipose-derived stem cells for clinical applications

脂肪干细胞(ADSCs)作为一种新的再生医学来源正受到越来越多的关注。ADSCs移植可促进周围神经损伤动物模型的功能恢复，但其促进神经再生的机制尚不清楚。在这项研究中，我们揭示了ADSCs促进周围神经再生的部分机制是通过旁分泌营养因子，而与供体年龄或来源解剖部位无关。这些结果表明，供体年龄和来源解剖部位不影响ADSCs的行为，使我们能够在广泛的年龄范围内安全有效地临床应用ADSCs。通过ADSC动力学的报告荧光蛋白随时间监测分化为Schwann细胞的结果，移植细胞在移植后3周被证实存活，尽管向Schwann细胞的分化尚未得到证实。这些结果表明，ADSC不是在特定的细胞环境中分化雪旺细胞，而是作为产生和释放神经再生相关因子的分子工厂来促进周围神经再生。我们还证明了分化的ADSC(DADSC)和未分化的ADSC(UADSC)具有相似的支持周围神经再生的能力，提示uADSC可以作为抗周围神经损伤的自体细胞治疗的替代来源。

Adipose-derived stem cells (ADSCs) are attracting increased attention as a novel source in regenerative medicine. Transplantation of ADSCs promotes functional recovery in animal models of peripheral nerve injury, but the mechanism of enhanced nerve regeneration remains to be elucidated. In this study, we revealed that ADSCs promote peripheral nerve regeneration partly through paracrine secretion of trophic factors and regardless of donor age or anatomic site of origin. These results suggested that donor age and the anatomic site of origin don’t influence the behavior of ADSCs and allow us safe and effective clinical application of ADSCs in in a wide age range.As a result of the monitoring of differentiation into Schwann cells with time with the reporter fluorescent protein for kinetics of ADSC, the survival of transplanted cells 3 weeks after transplantation was confirmed, although differentiation into Schwann cells was not confirmed. These results indicated that ADSC contributes to peripheral nerve regeneration by acting as a molecular factory producing and releasing nerve regeneration-related factors rather than by differentiating Schwann cells in a particular kind of cellular environment (niche) We also demonstrated that both differentiated ADSC(dADSC) and undifferentiated ADSC (uADSC) exhibited comparable ability to support peripheral nerve regeneration, suggesting that uADSC can be an alternative source for autologous cell therapy against peripheral nerve injury.