Journal
EXPERIMENTAL NEUROLOGY
Volume 216, Issue 1, Pages 47-55Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2008.11.010
Keywords
Angiogenesis; Regeneration; Stem and progenitor cells; Stroke; Transplantation
Categories
Funding
- Japanese Ministry of Education, Science, Sports and Culture [16390414, 20390388]
- National Multiple Sclerosis Society (U.S.A) [RG2135, CA1009A10]
- National Institutes of Health [NS43432]
- Medical and Rehabilitation and Development Research Services of the Department of Veterans Affairs
- Grants-in-Aid for Scientific Research [20390388, 16390414] Funding Source: KAKEN
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Intravenous transplantation of human mesenchymal stem cells (hMSCs) expanded from adult bone marrow ameliorates functional deficits in rat cerebral infarction models. Several hypotheses to account for the therapeutic mechanisms have been suggested, but angiogenesis is thought to be of critical importance. Recently, we have reported the therapeutic benefits of hMSCs which have been transfected with the angiopoietin-1 gene in a rat permanent middle cerebral artery occlusion (MCAO) model. To potentially enhance the therapeutic effects of angiopoietin-1 gene-modified hMSC (Ang-hMSC), we transfected hMSCs with the angiopoietin-1 gene and the VEGF gene, and investigated whether the combination of Ang-1 and VEGF gene-modified hMSCs (Ang-VEGF-hMSC) contribute to functional recovery in a rat MCAO model. We induced MCAO using intraluminal vascular occlusion, and hMSCs, Ang-hMSCs, VEGF-hMSCs or Ang-VEGF-hMSCs were intravenously infused 6 h later. MRI and behavioral analyses revealed that rats receiving Ang-VEGF-hMSCs showed the greatest structural-functional recovery as compared to the other groups. These results suggest that intravenous administration of hMSCs transfected with the angiopoietin-1 and VEGF gene using a fiber-mutant adenovirus vector may represent a new strategy for the treatment of ischemia. (C) 2008 Elsevier Inc. All rights reserved.
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