Adipose-Derived Stem Cells Produce Factors Enhancing Peripheral Nerve Regeneration: Influence of Age and Anatomic Site of Origin

Adipose-Derived Stem Cells Produce Factors Enhancing Peripheral Nerve Regeneration: Influence of Age and Anatomic Site of Origin
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DOI:
10.1089/scd.2011.0403
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发表时间:
2012-07-01
影响因子:
4
通讯作者:
Fushiki, Shinji
Fushiki, Shinji
中科院分区:
医学3区
文献类型:
--
作者:
Sowa, Yoshihiro;Imura, Tetsuya;Fushiki, Shinji

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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。此外,重要的是要检查ADSC的支持功能是否依赖于供体年龄或解剖部位的起源。在这项研究中,我们研究了由小鼠ADSCs产生的因子对体外培养的雪旺细胞(SC)和背根神经节(DRG)神经元的影响,并比较了来自不同年龄和不同解剖区域的ADSCs之间的这些影响。ADSC衍生的可溶性因子支持SC的存活和增殖,并促进DRG神经元中的轴突生长。这些有益效果远远上级来自3 T3-L1细胞的因子,并且与SC和星形胶质细胞(AC)衍生的因子相当。来自不同来源的ADSC类似地保留了它们的神经营养活性。实时逆转录-聚合酶链反应和酶联免疫吸附测定分析表明,ADSCs产生各种生长因子,其中一些比SC和AC更丰富。这些结果表明,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。
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 addition, it is important to examine whether the supportive functions of ADSCs are dependent on donor age or anatomic site of origin. In this study, we examined the effects of factors produced by mouse ADSCs on Schwann cells (SCs) and dorsal root ganglion (DRG) neurons in vitro and compared these effects among ADSCs from donors of different age and from different anatomic regions. ADSC-derived soluble factors supported survival and proliferation of SCs and promoted neurite outgrowth in DRG neurons. These beneficial effects were far superior to that of factors from 3T3-L1 cells and comparable to those of SC- and astrocyte (AC)-derived factors. ADSCs from different sources similarly retained their neurotrophic activity. Real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay analyses demonstrated that ADSCs produced various growth factors, some of which were more abundant than in SCs and ACs. These results suggest that ADSCs promote peripheral nerve regeneration partly through paracrine secretion of trophic factors and regardless of donor age or anatomic site of origin.