Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan.
Cytotherapy. 2011 Jul;13(6):675-85. doi: 10.3109/14653249.2010.549122. Epub 2011 Jan 13.
Transplantation of mesenchymal stromal cells (MSC) derived from bone marrow (BM) or adipose tissue is expected to become a cell therapy for stroke. The present study compared the therapeutic potential of adipose-derived stem cells (ASC) with that of BM-derived stem cells (BMSC) in a murine stroke model.
ASC and BMSC were isolated from age-matched C57BL/6J mice. These MSC were analyzed for growth kinetics and their capacity to secrete trophic factors and differentiate toward neural and vascular cell lineages in vitro. For in vivo study, ASC or BMSC were administrated intravenously into recipient mice (1 × 10(5) cells/mouse) soon after reperfusion following a 90-min middle cerebral artery occlusion. Neurologic deficits, the degree of infarction, expression of factors in the brain, and the fate of the injected cells were observed.
ASC showed higher proliferative activity with greater production of vascular endothelial cell growth factor (VEGF) and hepatocyte growth factor (HGF) than BMSC. Furthermore, in vitro conditions allowed ASC to differentiate into neural, glial and vascular endothelial cells. ASC administration showed remarkable attenuation of ischemic damage, although the ASC were not yet fully incorporated into the infarct area. Nonetheless, the expression of HGF and angiopoietin-1 in ischemic brain tissue was significantly increased in ASC-treated mice compared with the BMSC group.
Compared with BMSC, ASC have great advantages for cell preparation because of easier and safer access to adipose tissue. Taken together, our findings suggest that ASC would be a more preferable source for cell therapy for brain ischemia than BMSC.
骨髓（BM）或脂肪组织来源的间充质基质细胞（MSC）的移植有望成为中风的细胞治疗方法。本研究比较了脂肪来源的干细胞（ASC）与骨髓来源的干细胞（BMSC）在小鼠中风模型中的治疗潜力。
从年龄匹配的 C57BL/6J 小鼠中分离 ASC 和 BMSC。分析这些 MSC 的体外生长动力学及其分泌神经营养因子的能力，并向神经和血管细胞谱系分化。在体内研究中，在再灌注后 90 分钟大脑中动脉闭塞后，将 ASC 或 BMSC 静脉内给予接受者小鼠（1×10(5)细胞/只）。观察神经功能缺损、梗死程度、脑内因子的表达和注射细胞的命运。
与 BMSC 相比，ASC 具有更高的增殖活性，产生更多的血管内皮细胞生长因子（VEGF）和肝细胞生长因子（HGF）。此外，体外条件允许 ASC 分化为神经、胶质和血管内皮细胞。尽管 ASC 尚未完全整合到梗死区域，但 ASC 给药可显著减轻缺血损伤。然而，与 BMSC 组相比，在 ASC 治疗的小鼠中，缺血脑组织中的 HGF 和血管生成素-1 的表达明显增加。
与 BMSC 相比，ASC 具有更大的细胞制备优势，因为更容易和更安全地获得脂肪组织。综上所述，我们的研究结果表明，与 BMSC 相比，ASC 可能是脑缺血细胞治疗的更理想来源。
