Department of Neurosurgery and Stanford Stroke Center, Stanford Institute for Neuro-Innovation and Translational Neurosciences, Stanford University School of Medicine, Stanford, California 94305-5487, USA.
Stem Cells. 2011 Feb;29(2):274-85. doi: 10.1002/stem.584.
Cell transplantation offers a novel therapeutic strategy for stroke; however, how transplanted cells function in vivo is poorly understood. We show for the first time that after subacute transplantation into the ischemic brain of human central nervous system stem cells grown as neurospheres (hCNS-SCns), the stem cell-secreted factor, human vascular endothelial growth factor (hVEGF), is necessary for cell-induced functional recovery. We correlate this functional recovery to hVEGF-induced effects on the host brain including multiple facets of vascular repair and its unexpected suppression of the inflammatory response. We found that transplanted hCNS-SCns affected multiple parameters in the brain with different kinetics: early improvement in blood-brain barrier integrity and suppression of inflammation was followed by a delayed spatiotemporal regulated increase in neovascularization. These events coincided with a bimodal pattern of functional recovery, with, an early recovery independent of neovascularization, and a delayed hVEGF-dependent recovery coincident with neovascularization. Therefore, cell transplantation therapy offers an exciting multimodal strategy for brain repair in stroke and potentially other disorders with a vascular or inflammatory component.
细胞移植为中风提供了一种新的治疗策略；然而，人们对移植细胞在体内的作用知之甚少。我们首次表明，在亚急性移植到缺血性大脑的神经球培养的人中枢神经系统干细胞（hCNS-SCns）后，干细胞分泌的因子，人血管内皮生长因子（hVEGF），对于细胞诱导的功能恢复是必要的。我们将这种功能恢复与 hVEGF 对宿主大脑的影响相关联，包括血管修复的多个方面及其对炎症反应的意外抑制。我们发现，移植的 hCNS-SCns 以不同的动力学影响大脑中的多个参数：早期改善血脑屏障的完整性和抑制炎症，随后是延迟的时空调节增加新血管生成。这些事件与功能恢复的双峰模式一致，早期恢复与新血管生成无关，而与新血管生成一致的延迟 hVEGF 依赖性恢复。因此，细胞移植治疗为中风和其他可能具有血管或炎症成分的疾病的脑修复提供了一种令人兴奋的多模式策略。
