GLIAL DIFFERENTIATION OF HUMAN ADIPOSE-DERIVED STEM CELLS: IMPLICATIONS FOR CELL-BASED TRANSPLANTATION THERAPY
GLIAL DIFFERENTIATION OF HUMAN ADIPOSE-DERIVED STEM CELLS: IMPLICATIONS FOR CELL-BASED TRANSPLANTATION THERAPY
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DOI：
10.1016/j.neuroscience.2012.12.066
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发表时间：
2013-04-16
期刊：
影响因子：
3.3
通讯作者：
Hosokawa, K.
中科院分区：
文献类型：
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作者：
Tomita, K.;Madura, T.;Hosokawa, K.
越来越多的证据表明，脂肪干细胞（adipose-derived stem cells，ASCs）可以转分化为雪旺细胞（Schwann cell，SC）样细胞，促进神经再生，为外周神经损伤和神经退行性疾病的治疗提供了新的细胞移植治疗方法。为了将这些结果应用于临床，建立人ASC（hASC）向Sc表型的分化是非常重要的。在这项研究中，我们研究了从健康供体的皮下脂肪组织中获得的hASC。通过胶质细胞生长因子的混合物，我们将它们分化为雪旺细胞样细胞（dhASCs）。然后，我们评估了它们在体外和体内充当雪旺细胞的能力，并将它们与原代人类雪旺细胞（hSCs）进行了比较。酶联免疫吸附试验表明，dhASCs分泌脑源性神经营养因子（BDNF）/神经生长因子（NGF）在相当的水平，和胶质细胞源性神经营养因子（GDNF）的水平甚至高于hSCs，而未分化的hASCs（uhASCs）分泌这些神经营养因子的低水平。在与NG 108 -15神经元细胞的共培养中，我们发现dhASC和hSC均显著增加具有神经突的细胞的百分比、神经突长度和每个神经元的神经突数量，而uhASC仅增加具有神经突的细胞的百分比。最后，我们将绿色荧光蛋白（GFP）标记的hASCs移植到无胸腺裸大鼠的胫神经中。移植后8周，移植的hASCs与PGP9.5阳性轴突和髓鞘碱性蛋白（MBP）阳性髓鞘密切相关。定量分析显示，与uhASC移植相比，dhASC移植导致存活率和髓鞘形成率显著提高（分别增加7倍和10倍）。这些发现表明，hASCs参与支持和髓鞘再生轴突，从而在体内实现了完全的胶质细胞分化。总之，hASCs可以分化成SC样细胞，具有强大的能力，分泌神经营养因子，以及在体内形成髓鞘。这些发现使hASCs成为一个有趣的前景为基础的细胞移植治疗各种周围神经疾病。(C)2013年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Increasing evidence has shown that adipose-derived stem cells (ASCs) could transdifferentiate into Schwann cell (SC)-like cells to enhance nerve regeneration, suggesting potential new cell-based transplantation therapy for peripheral nerve injuries and neurodegenerative disorders. For the implementation of these results to the clinical setting, it is of great importance to establish the differentiation of human ASCs (hASCs) into a Sc phenotype. In this study, we studied hASCs obtained from subcutaneous fat tissue of healthy donors. By a mixture of glial growth factors we differentiated them into Schwann cell-like cells (dhASCs). We then assessed their ability to act as Schwann cells in vitro and in vivo and also compared them with primary human Schwann cells (hSCs). Enzyme-linked immunosorbent assay showed that dhASCs secreted brain-derived neurotrophic factor (BDNF)/nerve growth factor (NGF) at a comparable level, and glial cell-derived neurotrophic factor (GDNF) at a level even higher than hSCs, whereas undifferentiated hASCs (uhASCs) secreted low levels of these neurotrophic factors. In co-culture with NG108-15 neuronal cells we found that both dhASCs and hSCs significantly increased the percentage of cells with neurites, the neurite length, and the number of neurites per neuron, whereas uhASCs increased only the percentage of cells with neurites. Finally, we transplanted green fluorescent protein (GFP)-labeled hASCs into the crushed tibial nerve of athymic nude rats. The transplanted hASCs showed a close association with PGP9.5-positive axons and myelin basic protein (MBP)-positive myelin at 8 weeks after transplantation. Quantitative analysis revealed that dhASCs transplantation resulted in significantly improved survival and myelin formation rates (a 7-fold and a 10-fold increase, respectively) as compared with uhASCs transplantation. These findings suggest that hASCs took part in supporting and myelinating regenerating axons, and thus have achieved full glial differentiation in vivo. In conclusion, hASCs can differentiate into SC-like cells that possess a potent capacity to secrete neurotrophic factors as well as to form myelin in vivo. These findings make hASCs an interesting prospect for cell-based transplantation therapy for various peripheral nerve disorders. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.