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Transplanted Stem Cell-Secreted VEGF Effects Post-Stroke Recovery, Inflammation, and Vascular Repair.

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Transplanted Stem Cell-Secreted VEGF Effects Post-Stroke Recovery, Inflammation, and Vascular Repair. Stem cells (Dayton, Ohio) Horie, N., Pereira, M. P., Niizuma, K., Sun, G., Keren-Gill, H., Encarnacion, A., Shamloo, M., Hamilton, S. A., Jiang, K., Huhn, S., Palmer, T. D., Bliss, T. M., Steinberg, G. K. 2011

Abstract

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 sub-acute transplantation into the ischemic brain of human central nervous system stem cells grown as neurospheres (hCNS-SCns), the stem cell-secreted factor, human VEGF (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 (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.

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