Disparate host response and donor survival after the transplantation of mesenchymal or neuroectodermal cells to the intact rodent brain
Disparate host response and donor survival after the transplantation of mesenchymal or neuroectodermal cells to the intact rodent brain
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DOI：
10.1097/01.tp.0000288185.09601.4d
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发表时间：
2007-12-15
期刊：
影响因子：
6.2
通讯作者：
Woodbury, Dale
中科院分区：
文献类型：
--
作者：
Coyne, Thomas M.;Marcus, Akiva J.;Woodbury, Dale
背景。为了避免与胚胎细胞来源相关的伦理和法律并发症，研究人员提出在神经移植策略中使用非神经供体来源。主要的候选来源包括自体骨髓基质细胞（MSCs）和成纤维细胞，它们是中胚层的衍生物。然而，我们最近报道了骨髓间充质干细胞移植到成人大脑后会被炎症反应迅速排斥。是否外在变量或内在间质特性刺激炎症和排斥是未知的。为了确定这些细胞在神经移植中的未来用途，我们现在对MSC移植到大脑进行了系统的分析。为了研究外部变量对移植的影响，在不同条件下培养表达绿色荧光蛋白（GFP）的大鼠间充质干细胞，将其立体定向移植到正常成年大鼠纹状体中，并比较供体存活和宿主反应。为了研究内在供体特征是否促进排斥反应，我们将50,000只表达gfp的大鼠间充质干细胞、成纤维细胞或星形胶质细胞立体定向移植到成年大鼠纹状体，并比较移植物的存活和宿主反应。无论术前培养条件如何，MSCs都引起了炎症反应，并在14天后被排斥，这表明急性排斥反应不是由培养条件介导的。间充质干细胞、成纤维细胞和星形胶质细胞移植物的比较显示，间充质衍生物，MSCs和成纤维细胞，引起炎症反应并迅速被排斥，而神经外胚层星形胶质细胞在没有炎症的情况下表现出强大的存活能力。我们的研究结果表明，间充质细胞的内在特征可能会刺激宿主炎症，因此可能不是移植到成人大脑的理想供体来源。
Background. To circumvent ethical and legal complications associated with embryonic cell sources, investigators have proposed the use of nonneural donor sources for use in neural transplantation strategies. Leading candidate sources include autologous marrow stromal cells (MSCs) and fibroblasts, which are mesodermal derivatives. However, we recently reported that MSCs transplanted to the adult brain are rapidly rejected by an inflammatory response. Whether extrinsic variables or intrinsic mesenchymal traits stimulated inflammation and rejection is unknown. To determine the future utility of these cells in neural transplantation, we-have now performed a systematic analysis of MSC transplantation to the brain.Methods. To examine the effects of extrinsic variables on transplantation, green fluorescent protein (GFP) -expressing rat MSCs, cultured under distinct conditions, were transplanted stereotactically to the normal adult rat striatum, and donor survival and the host response was compared. To examine whether intrinsic donor traits promoted rejection, 50,000 GFP-expressing rat MSCs, fibroblasts, or astrocytes were transplanted stereotactically to the adult rat striatum and graft survival and the host response was compared.Results. Irrespective of preoperative culture conditions, MSCs elicited an inflammatory response and were rejected by 14 days, indicating acute rejection was not mediated by culture conditions. Comparison of MSC, fibroblast, or astrocyte grafts revealed that mesenchymal derivatives, MSCs and fibroblasts, elicited an inflammatory response and were rapidly rejected, whereas neuroectodermal astrocytes demonstrated robust survival in the absence of inflammation.Conclusions. Our findings suggest that intrinsic characteristics of mesenchymal cells may stimulate host inflammation, and thus may not represent an ideal donor source for transplantation to the adult brain.