抄録
Cell transplantation offers a novel therapeutic strategy for stroke; however, how transplanted cells function in vivo is poorly understood. In this study, we test the hypothesis that grafted human neural stem/progenitor cells enhance the endogenous repair that occurs after stroke. Moreover, we summarize the results from present pre-clinical and clinical studies and focus on the potential mechanisms (angiogenesis, BBB integrity, axonal sprouting, dendritic branching, and inflammation) in functional recovery after cell transplantation.
We found that transplanted cells affected multiple parameters in the brain with different kinetics: early improvement in blood-brain barrier (BBB) integrity and suppression of inflammation was followed by a delayed spatio-temporal regulated increase in neovascularization. These events coincided with a bi-modal pattern of functional recovery: an early recovery independent of neovascularization, and a delayed hVEGF-dependent recovery coincident with neovascularization. Therefore, cell transplantation therapy offers an exciting multi-modal strategy for brain repair in stroke and potentially other disorders with a vascular or inflammatory component. We also demonstrated that transplanted cells enhance axonal sprouting and dendritic branching of host neurons after stroke, and that these plasticity changes correlated with cell-induced recovery.
The Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) meeting was organized to bring together clinical and basic researchers with industry and regulatory representatives to assess the critical issues in the field and to create a framework to guide future investigations.
