Anatomical Site Influences the Differentiation of Adipose-Derived Stem Cells for Schwann-Cell Phenotype and Function
Anatomical Site Influences the Differentiation of Adipose-Derived Stem Cells for Schwann-Cell Phenotype and Function
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DOI：
10.1002/glia.21145
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发表时间：
2011-05-01
期刊：
影响因子：
6.2
通讯作者：
Haycock, John W.
中科院分区：
文献类型：
--
作者：
Kaewkhaw, Rossukon;Scutt, Andy M.;Haycock, John W.
脂肪干细胞是治疗周围神经损伤的重要来源，与骨髓间充质干细胞或自体雪旺细胞相比具有明显的临床优势。然而，脂肪供体部位与分化的ASC表型和功能之间的关系目前尚不清楚。本工作系统地研究了取自三个解剖部位的ASCs的分化：(I)皮下；(Ii)肾周；(Iii)附睾部脂肪组织。我们发现ASC来源是免疫表型、多系分化、雪旺细胞蛋白表达和旁分泌刺激神经元生长能力的主要决定因素。肾周脂肪分化的ASCs表达S100β、胶质纤维酸性蛋白(GFAP)和p75NGFR，而皮下脂肪和附睾脂分化的ASCs仅表达S100β、GFAP和p75NGFR。分化的ASCs与NG108-15神经细胞共培养表明，不同来源的ASCs均能刺激轴突生长和数量，但皮下脂肪和肾周脂肪与附睾脂分化的ASCs效果最好，这与高脑源性神经营养因子/神经生长因子和低神经营养素-3水平有关。因此，ASCs可以从不同的解剖位置获得，这决定了雪旺细胞的分化和功能程度。因此，这项工作不仅对修复周围神经损伤的ASCs的局部治疗有意义，而且对ASC在相关干细胞疗法中的应用也有广泛的意义。(C)2011年Wiley-Liss，Inc.
Considerable attention has recently been given to adipose-derived stem cells (ASCs) as an important source for differentiation to Schwann cells in the treatment of peripheral nerve injury, with considerable clinical advantages over the use of mesenchymal stem cells derived from bone marrow or autologous Schwann cells. However, the relationship between adipose donor site and differentiated ASC phenotype and function is presently unknown. This work systematically studied the differentiation of ASCs harvested from three anatomical sites: (i) subcutaneous; (ii) perinephric; and (iii) epididymal adipose tissue. We show that ASC source is a major determining factor of immunophenotype, multilineage differentiation, Schwann-cell protein expression, and paracrine ability to stimulate neuronal growth. Upregulation of S100 beta, glial fibrillary acidic protein (GFAP), and p75NGFR was observed in differentiated ASCs from perinephric fat tissue, while only the expression of S100 beta or GFAP and p75NGFR was elevated in differentiated ASCs from subcutaneous or epididymal fat tissue. Although the co-culture of differentiated ASCs with NG108-15 neuronal cells demonstrated that ASCs from each source could stimulate neurite outgrowth and number, differentiated ASCs from subcutaneous and perinephric fat versus epididymal fat were most effective, which was attributed to high-brain-derived neurotropic factor/nerve growth factor and low-neurotrophin-3 levels. Thus, ASCs can be obtained from different anatomical locations, and this determines Schwann-cell phenotype upon differentiation and extent of function. This work is therefore of relevance in local therapeutic delivery of ASCs for the repair of peripheral nerve injury, but also in the broader context of ASC use in related stem-cell therapies. (c) 2011 Wiley-Liss, Inc.