In Vitro and In Vivo Characterization of Neurally Modified Mesenchymal Stem Cells Induced by Epigenetic Modifiers and Neural Stem Cell Environment
In Vitro and In Vivo Characterization of Neurally Modified Mesenchymal Stem Cells Induced by Epigenetic Modifiers and Neural Stem Cell Environment
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DOI：
10.1089/scd.2007.0212
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发表时间：
2008-12-01
影响因子：
4
通讯作者：
Gennarelli, Thomas A.
中科院分区：
文献类型：
--
作者：
Alexanian, Arshak R.;Maiman, Dennis J.;Gennarelli, Thomas A.
间充质干细胞（MSC）介导的组织再生是治疗多种神经退行性疾病和中枢神经系统创伤性损伤的一种很有前途的策略。骨髓间充质干细胞作为治疗剂具有很大的潜力，因为它们易于分离和扩增，并且能够产生包括神经细胞在内的各种细胞类型。最近，我们开发了一种高效的方法，从小鼠骨髓来源的MSCs中产生神经干细胞样细胞和神经前体细胞样细胞，这些细胞最终在体外分化为神经元和胶质样细胞。本研究的目的是进一步阐明神经诱导间充质干细胞（NI-MSCs）在移植到大鼠完整脊髓后的神经表达谱及其保留神经分化潜能的能力。为此，我们通过免疫细胞化学、Western blot、ELISA和免疫组织化学进一步表征了NI-MSCs的体外和体内特性。免疫细胞化学数据显示，NI-MSCs表达多种成熟的神经标志物，如B3T、GFAP MAP-2、NF-200和NeuN，通过Western blot证实。ELISA数据显示，NI-MSCs释放神经生长因子（NGF）和脑源性神经营养因子（BDNF）。体内研究表明，移植的NI-MSCs在移植到完整的脊髓后存活，并产生表达神经标志物的细胞。所有这些数据表明，通过最近发展的方法诱导的神经修饰间充质干细胞可能是替代受损脊髓中受损神经元和胶质细胞的潜在细胞来源，和/或促进宿主组织的细胞存活和轴突生长。
Mesenchymal stem cell (MSC)-mediated tissue regeneration is a promising strategy to treat several neurodegenerative diseases and traumatic injuries of the central nervous system. Bone marrow MSCs have great potential as therapeutic agents, since they are easy to isolate and expand and are capable of producing various cell types, including neural cells. Recently we developed a highly efficient methodology to produce neural stem-like and neural precursor-like cells from mice bone marrow-derived MSCs that eventually differentiate into neuronaland glial-like cells in vitro. The aim of this study is to further elucidate neural expression profile of neurally induced mesenchymal stem cells (NI-MSCs) and their ability to retain neural differentiation potential when grafted into the intact spinal cord of rats. To this end, we further characterized in vitro and in vivo properties of NI-MSCs by immunocytochemistry, Western blot, ELISA, and immunohistochemistry. Immunocytochemical data demonstrated that NI-MSCs express several mature neural markers such as B3T, GFAP MAP-2, NF-200, and NeuN, which were confirmed through Western blot. ELISA data showed that NI-MSCs release nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). In vivo studies demonstrated that grafted NI-MSCs survived after transplantation into intact spinal cord and produced cells that expressed neural markers. All these data suggest that neurally modified MSCs, induced by recently developed methodology, could be a potential source of cells to replace damaged neurons and glia in injured spinal cord, and/or to promote cell survival and axonal growth of host tissue.