Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy

Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy
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DOI:
10.3109/14653249.2010.549122
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发表时间:
2011-07-01
期刊:
影响因子:
4.5
通讯作者:
Iwama, Toru
Iwama, Toru
中科院分区:
医学3区
文献类型:
--
作者:
Ikegame, Yuka;Yamashita, Kentaro;Iwama, Toru

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背景目标。骨髓或脂肪组织来源的间充质干细胞(MSC)移植有望成为治疗脑卒中的细胞疗法。本研究比较了脂肪源性干细胞(ASC)与骨髓源性干细胞(BMSC)在小鼠中风模型中的治疗潜力。方法.从年龄匹配的C57 BL/6 J小鼠中分离ASC和BMSC。分析这些MSC的生长动力学及其分泌营养因子和体外向神经和血管细胞系分化的能力。对于体内研究,在大脑中动脉闭塞90分钟后再灌注后不久,将ASC或BMSC静脉内给予受体小鼠(1 × 105个细胞/小鼠)。观察神经功能缺损、梗死程度、脑中因子的表达和注射细胞的命运。结果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)比BMSC。此外,在体外条件下允许ASC分化为神经,神经胶质和血管内皮细胞。ASC给药显示出显著的缺血性损伤衰减,尽管ASC尚未完全并入梗死区域。然而,与BMSC组相比,ASC治疗的小鼠缺血脑组织中HGF和血管生成素-1的表达显著增加。结论.与BMSC相比,ASC更容易、更安全地从脂肪组织中获取细胞,具有很大的优势。综上所述,我们的研究结果表明,ASC将是一个更可取的来源细胞治疗脑缺血比骨髓基质细胞。
Background aims. 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. Methods. 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 x 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. Results. 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. Conclusions. 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.