N.H. and M.P.P. contributed equally to this article.
Article first published online: 24 FEB 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 2, pages 274–285, February 2011
How to Cite
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. and Steinberg, G. K. (2011), Transplanted Stem Cell-Secreted Vascular Endothelial Growth Factor Effects Poststroke Recovery, Inflammation, and Vascular Repair. STEM CELLS, 29: 274–285. doi: 10.1002/stem.584
Author contributions: N.H.: design, collection, and assembly of data, data analysis and interpretation, manuscript writing; M.P.P.: design, collection, and assembly of data, data analysis and interpretation, manuscript writing; K.N.: collection and assembly of data, data analysis and interpretation; G.S.: collection of data; H.K.-G.: collection of data; A.E.: collection of data; M.S.: collection of data; S.A.H.: statistical analysis advice; K.J.: collection of data; S.H.: provision of study material, manuscript writing; T.D.P.: data analysis and interpretation; T.M.B.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript; G.K.S.: financial support, design, data interpretation, manuscript writing, final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS January 14, 2011.
- Issue published online: 24 FEB 2011
- Article first published online: 24 FEB 2011
- Accepted manuscript online: 14 JAN 2011 12:27PM EST
- Manuscript Accepted: 23 NOV 2010
- Manuscript Received: 5 MAR 2010
- National Institutes of Health National Institute of Neurological Disorders and Stroke. Grant Numbers: NS058784, NS27292, NS37520
- William Randolph Hearst Foundation, Bernard and Ronni Lacroute, Russell and Elizabeth Siegelman, and the Edward E. Hills Fund
- Ministry of Education and Science of Spain (reference 2007-1219)
- Blood-brain barrier;
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. STEM CELLS 2011;29:274–285