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

脂肪源性干细胞（ADSCs）作为再生医学的一种新来源正引起越来越多的关注。脂肪干细胞移植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仍有待阐明。在这项研究中，我们发现，脂肪干细胞促进周围神经再生部分通过旁分泌的营养因子，无论供体年龄或解剖部位的起源。这些结果表明，供体年龄和来源的解剖部位不影响ADSC的行为，并且允许我们在广泛的年龄范围内安全有效地临床应用ADSC。由于用ADSC动力学的报告荧光蛋白监测随着时间向雪旺细胞分化的结果，证实了移植后3周移植细胞的存活，尽管没有证实向许旺细胞的分化。这些结果表明，ADSC通过充当产生和释放神经再生相关因子的分子工厂而不是通过在特定种类的细胞环境（生态位）中分化施万细胞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）都表现出相当的支持周围神经再生的能力，这表明uADSC可以是针对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.