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Translational and Clinical Research
Article first published online: 1 JUN 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 7, pages 1292–1302, July 2010
How to Cite
Nakano-Doi, A., Nakagomi, T., Fujikawa, M., Nakagomi, N., Kubo, S., Lu, S., Yoshikawa, H., Soma, T., Taguchi, A. and Matsuyama, T. (2010), Bone Marrow Mononuclear Cells Promote Proliferation of Endogenous Neural Stem Cells Through Vascular Niches After Cerebral Infarction. STEM CELLS, 28: 1292–1302. doi: 10.1002/stem.454
Author contributions: A.N.-D.: collection and assembly of data, data analysis and interpretation, final approval of manuscript; T.N.: conception and design, financial support, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; M.F. and N.N.: collection and assembly of data; S.K.: provision of study material; S.L., H.Y., and T.S.: data analysis and interpretation; A.T.: conception and design, data analysis and interpretation, final approval of manuscript; T.M.: conception and design, financial support, data analysis and interpretation, final approval of manuscript. A.N-D. and T.N. contributed equally to this article.
First published online in STEM CELLSEXPRESS June 1, 2010.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue published online: 20 JUL 2010
- Article first published online: 1 JUN 2010
- Manuscript Accepted: 18 MAY 2010
- Manuscript Received: 5 JAN 2010
- Ministry of Education, Culture, Sports, Science and Technology. Grant Numbers: 21700363, 21500359
- Hyogo Science and Technology Association
- Takeda Science Foundation, 2009
- Bone marrow mononuclear cells;
- Neural stem/progenitor cells;
- Vascular niches;
- Endothelial cells;
- Ischemic stroke
Increasing evidence shows that administration of bone marrow mononuclear cells (BMMCs) is a potential treatment for various ischemic diseases, such as ischemic stroke. Although angiogenesis has been considered primarily responsible for the effect of BMMCs, their direct contribution to endothelial cells (ECs) by being a functional elements of vascular niches for neural stem/progenitor cells (NSPCs) has not been considered. Herein, we examine whether BMMCs affected the properties of ECs and NSPCs, and whether they promoted neurogenesis and functional recovery after stroke. We compared i.v. transplantations 1 × 106 BMMCs and phosphate-buffered saline in mice 2 days after cortical infarction. Systemically administered BMMCs preferentially accumulated at the postischemic cortex and peri-infarct area in brains; cell proliferation of ECs (angiogenesis) at these regions was significantly increased in BMMCs-treated mice compared with controls. We also found that endogenous NSPCs developed in close proximity to ECs in and around the poststroke cortex and that ECs were essential for proliferation of these ischemia-induced NSPCs. Furthermore, BMMCs enhanced proliferation of NSPCs as well as ECs. Proliferation of NSPCs was suppressed by additional treatment with endostatin (known to inhibit proliferation of ECs) following BMMCs transplantation. Subsequently, neurogenesis and functional recovery were also promoted in BMMCs-treated mice compared with controls. These results suggest that BMMCs can contribute to the proliferation of endogenous ischemia-induced NSPCs through vascular niche regulation, which includes regulation of endothelial proliferation. In addition, these results suggest that BMMCs transplantation has potential as a novel therapeutic option in stroke treatment. STEM CELLS 2010;28:1292–1302