Transplantation of Predifferentiated Adipose-Derived Stromal Cells for the Treatment of Spinal Cord Injury
Transplantation of Predifferentiated Adipose-Derived Stromal Cells for the Treatment of Spinal Cord Injury
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DOI：
10.1007/s10571-011-9712-3
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发表时间：
2011-10-01
影响因子：
4
通讯作者：
Sykova, Eva
中科院分区：
文献类型：
--
作者：
Arboleda, David;Forostyak, Serhiy;Sykova, Eva
脂肪源性基质细胞（ASC）是神经系统疾病（如脊髓损伤（SCI））基于细胞的治疗的干细胞的替代来源。在本研究中，我们预分化的ASCs（pASCs），并比较其行为与幼稚ASCs在体外和移植到大鼠与球囊诱导的压迫性病变。移植前先将ASCs预分化成球形，脊髓损伤后1周将pASCs或ASCs分别注入脊髓内。使用行为学、组织学和电生理学方法评估细胞的命运和大鼠的功能结果。体外pASCs的免疫组织化学分析显示NCAM、NG 2、S100和p75的表达。神经诱导后不同时间的定量RT-PCR显示神经胶质细胞标志物NG 2和p75以及神经前体细胞标志物NCAM和Nestin的表达上调。pASC的膜片钳分析揭示了三种不同类型的膜电流;然而，没有一种是快速激活的Na（+）电流，表明成熟的神经元表型。在BBB运动试验中观察到pASC和ASC移植组的显著改善。在体内，pASCs比ASCs存活得更好，并与宿主组织密切相互作用，包裹宿主轴突和少突胶质细胞。部分移植细胞呈NG 2或CD 31阳性，但未检测到神经元标志物。ASCs的预分化通过促进对裸露轴突的保护在SCI修复中起着有益的作用;然而，两组的功能改善是相当的，表明修复主要是通过旁分泌机制诱导的。
Adipose-derived stromal cells (ASCs) are an alternative source of stem cells for cell-based therapies of neurological disorders such as spinal cord injury (SCI). In the present study, we predifferentiated ASCs (pASCs) and compared their behavior with na < ve ASCs in vitro and after transplantation into rats with a balloon-induced compression lesion. ASCs were predifferentiated into spheres before transplantation, then pASCs or ASCs were injected intraspinally 1 week after SCI. The cells' fate and the rats' functional outcome were assessed using behavioral, histological, and electrophysiological methods. Immunohistological analysis of pASCs in vitro revealed the expression of NCAM, NG2, S100, and p75. Quantitative RT-PCR at different intervals after neural induction showed the up-regulated expression of the glial markers NG2 and p75 and the neural precursor markers NCAM and Nestin. Patch clamp analysis of pASCs revealed three different types of membrane currents; however, none were fast activating Na(+) currents indicating a mature neuronal phenotype. Significant improvement in both the pASC and ASC transplanted groups was observed in the BBB motor test. In vivo, pASCs survived better than ASCs did and interacted closely with the host tissue, wrapping host axons and oligodendrocytes. Some transplanted cells were NG2- or CD31-positive, but no neuronal markers were detected. The predifferentiation of ASCs plays a beneficial role in SCI repair by promoting the protection of denuded axons; however, functional improvements were comparable in both the groups, indicating that repair was induced mainly through paracrine mechanisms.