Potential of rat bone marrow-derived mesenchymal stem cells as vehicles for delivery of neurotrophins to the Parkinsonian rat brain
Potential of rat bone marrow-derived mesenchymal stem cells as vehicles for delivery of neurotrophins to the Parkinsonian rat brain
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DOI：
10.1016/j.brainres.2010.08.040
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发表时间：
2010-11-04
期刊：
影响因子：
2.9
通讯作者：
Dowd, Eilis
中科院分区：
文献类型：
--
作者：
Moloney, Teresa C.;Rooney, Gemma E.;Dowd, Eilis
与神经胶质细胞源性神经营养因子（GDNF）脑内递送相关的问题阻碍了其作为帕金森病神经保护疗法的进展。离体基因疗法，即在体外通过病毒转导细胞产生特定蛋白质，可以避免与将这种神经营养蛋白直接递送至大脑相关的一些问题。在这方面，骨髓间充质干细胞（MSC）为离体基因治疗提供了理想的细胞来源，因为它们很容易从自体来源分离，它们适合体外病毒转导和扩增，并且它们在大脑中具有低免疫原性和非致瘤性。因此，本研究的目的是。确定 GDNF 转导的 MSC 在帕金森病大鼠模型中的神经营养能力。在诱导纹状体内 6-羟基多巴胺损伤前 4 天，大鼠接受 GDNF 转导的 MSC 的纹状体内移植。定量酪氨酸羟化酶免疫组织化学染色显示，GDNF 转导的 MSC 能够在去神经纹状体中诱导显着的局部营养效应，这一点通过从剩余的多巴胺能末端向移植细胞产生的神经营养环境发芽来证明。这增强了间充质干细胞作为向帕金森病大脑输送神经营养素的载体的候选资格。 (C) 2010 Elsevier B.V. 保留所有权利。
Issues related to the intra-cerebral delivery of glial cell line-derived neurotrophic factor (GDNF) have hampered its progression as a neuroprotective therapy for Parkinson's disease. Ex vivo gene therapy, where cells are virally transduced in vitro to produce a specific protein, may circumvent some of the problems associated with direct delivery of this neurotrophin to the brain. In this regard, bone marrow-derived mesenchymal stem cells (MSCs) offer an ideal cell source for ex vivo gene therapy because they are easily isolated from autologous sources, they are amenable to viral transduction and expansion in vitro, and they are hypoimmunogenic and non-tumourigenic in the brain. Thus the aim of this study was to. determine the neurotrophic capacity of GDNF-transduced MSCs in a rat model of Parkinson's disease. Rats received intrastriatal transplants of GDNF-transduced MSCs 4days prior to induction of an intrastriatal 6-hydroxydopamine lesion. Quantitative tyrosine hydroxylase immunohistochemical staining revealed that GDNF-transduced MSCs were capable of inducing a pronounced local trophic effect in the denervated striatum which was evident by sprouting from the remaining dopaminergic terminals towards the neurotrophic milieu created by the transplanted cells. This strengthens the candidacy of MSCs as vehicles to deliver neurotrophins to the Parkinsonian brain. (C) 2010 Elsevier B.V. All rights reserved.