Kingham Paul J, Kalbermatten Daniel F, Mahay Daljeet, Armstrong Stephanie J, Wiberg Mikael, Terenghi Giorgio
Blond McIndoe Research Laboratories, The University of Manchester, Room 3.106 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Exp Neurol. 2007 Oct;207(2):267-74. doi: 10.1016/j.expneurol.2007.06.029. Epub 2007 Aug 2.
Experimentally, peripheral nerve repair can be enhanced by Schwann cell transplantation but the clinical application is limited by donor site morbidity and the inability to generate a sufficient number of cells quickly. We have investigated whether adult stem cells, isolated from adipose tissue, can be differentiated into functional Schwann cells. Rat visceral fat was enzymatically digested to yield rapidly proliferating fibroblast-like cells, a proportion of which expressed the mesenchymal stem cell marker, stro-1, and nestin, a neural progenitor protein. Cells treated with a mixture of glial growth factors (GGF-2, bFGF, PDGF and forskolin) adopted a spindle-like morphology similar to Schwann cells. Immunocytochemical staining and western blotting indicated that the treated cells expressed the glial markers, GFAP, S100 and p75, indicative of differentiation. When co-cultured with NG108-15 motor neuron-like cells, the differentiated stem cells enhanced the number of NG108-15 cells expressing neurites, the number of neurites per cell and the mean length of the longest neurite extended. Schwann cells evoked a similar response whilst undifferentiated stem cells had no effect. These results indicate adipose tissue contains a pool of regenerative stem cells which can be differentiated to a Schwann cell phenotype and may be of benefit for treatment of peripheral nerve injuries.
在实验中,施万细胞移植可增强周围神经修复,但临床应用受到供体部位发病率以及无法快速产生足够数量细胞的限制。我们研究了从脂肪组织分离的成体干细胞是否能分化为功能性施万细胞。大鼠内脏脂肪经酶消化产生快速增殖的成纤维细胞样细胞,其中一部分表达间充质干细胞标志物stro-1和神经祖细胞蛋白巢蛋白。用神经胶质生长因子混合物(GGF-2、bFGF、PDGF和福斯可林)处理的细胞呈现出类似于施万细胞的纺锤样形态。免疫细胞化学染色和蛋白质印迹表明,处理后的细胞表达神经胶质标志物GFAP、S100和p75,表明发生了分化。当与NG108-15运动神经元样细胞共培养时,分化的干细胞增加了表达神经突的NG108-15细胞数量、每个细胞的神经突数量以及最长神经突的平均长度。施万细胞也引发了类似反应,而未分化的干细胞则没有效果。这些结果表明脂肪组织含有一群可再生干细胞,它们可分化为施万细胞表型,可能有助于治疗周围神经损伤。