Alexanian Arshak R, Maiman Dennis J, Kurpad Shekar N, Gennarelli Thomas A
Neuroscience Research Laboratories, Department of Neurosurgery, Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295, USA.
Stem Cells Dev. 2008 Dec;17(6):1123-30. doi: 10.1089/scd.2007.0212.
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 neuronal- and 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.
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有前景的策略。骨髓间充质干细胞作为治疗剂具有巨大潜力,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方法,可从小鼠骨髓来源的间充质干细胞中产生神经干细胞样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样和神经胶质样细胞。本研究的目的是进一步阐明神经诱导的间充质干细胞(NI-MSCs)的神经表达谱及其移植到大鼠完整脊髓中时保留神经分化潜能的能力。为此,我们通过免疫细胞化学、蛋白质免疫印迹、酶联免疫吸附测定和免疫组织化学进一步表征了NI-MSCs的体外和体内特性。免疫细胞化学数据表明,NI-MSCs表达多种成熟的神经标志物,如B3T、GFAP MAP-2、NF-200和NeuN,这些通过蛋白质免疫印迹得到了证实。酶联免疫吸附测定数据显示,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,移植到完整脊髓中的NI-MSCs在移植后存活,并产生表达神经标志物的细胞。所有这些数据表明,通过最近开发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神经胶质细胞,和/或促进宿主组织细胞存活和轴突生长的潜在细胞来源。