Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Curr Stem Cell Res Ther. 2011 Dec;6(4):327-38. doi: 10.2174/157488811797904362.
The plasticity of neural stem/progenitor cells allows a variety of different responses to many environmental cues. In the past decade, significant research has gone into understanding the regulation of neural stem/progenitor cell properties, because of their promise for cell replacement therapies in adult neurological diseases. Both endogenous and grafted neural stem/progenitor cells are known to have the ability to migrate long distances to lesioned sites after brain injury and differentiate into new neurons. Several chemokines and growth factors, including stromal cell-derived factor-1 and vascular endothelial growth factor, have been shown to stimulate the proliferation, differentiation, and migration of neural stem/progenitor cells, and investigators have now begun to identify the critical downstream effectors and signaling mechanisms that regulate these processes. Both our own lab and others have shown that the extracellular matrix and matrix remodeling factors play a critical role in directing cell differentiation and migration of adult neural stem/progenitor cells within injured sites. Identification of these and other molecular pathways involved in stem cell homing into ischemic areas is vital for the development of new treatments. To ensure the best functional recovery, regenerative therapy may require the application of a combination approach that includes cell replacement, trophic support, and neural protection. Here we review the current state of our knowledge about endogenous adult and exogenous neural stem/progenitor cells as potential therapeutic agents for central nervous system injuries.
神经干细胞/祖细胞的可塑性使其能够对多种环境线索做出各种不同的反应。在过去的十年中，由于神经干细胞/祖细胞在成人神经疾病的细胞替代治疗中具有广阔的应用前景，人们对其特性的调控进行了大量研究。已知内源性和移植的神经干细胞/祖细胞具有向脑损伤后的损伤部位长距离迁移并分化为新神经元的能力。一些趋化因子和生长因子，包括基质细胞衍生因子-1 和血管内皮生长因子，已被证明可刺激神经干细胞/祖细胞的增殖、分化和迁移，研究人员现已开始鉴定调控这些过程的关键下游效应因子和信号机制。我们自己的实验室和其他实验室都表明，细胞外基质和基质重塑因子在指导损伤部位成年神经干细胞/祖细胞的细胞分化和迁移方面起着关键作用。鉴定这些和其他涉及干细胞归巢到缺血区域的分子途径对于开发新的治疗方法至关重要。为了确保最佳的功能恢复，再生疗法可能需要采用包括细胞替代、营养支持和神经保护在内的联合治疗方法。在这里，我们回顾了关于内源性成体和外源性神经干细胞/祖细胞作为中枢神经系统损伤潜在治疗剂的现有知识状况。
