Journal Article

Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia

H. Liu, O. Honmou, K. Harada, K. Nakamura, K. Houkin, H. Hamada and J. D. Kocsis

in Brain

Published on behalf of The Guarantors of Brain

Volume 129, issue 10, pages 2734-2745
ISSN: 0006-8950
Published online August 2006 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awl207
Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia

Show Summary Details

Preview

Intravenous delivery of mesenchymal stem cells (MSCs) prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischaemia models. Placental growth factor (PlGF) is angiogenic to impaired non-neural tissue. To test the hypothesis that PlGF contributes to the therapeutic benefits of MSC delivery in cerebral ischaemia, we compared the efficacy of systemic delivery of human MSCs (hMSCs) and hMSCs transfected with a fibre-mutant F/RGD adenovirus vector with a PlGF gene (PlGF-hMSCs). A permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament. hMSCs and PlGF-hMSCs were intravenously injected into the rats 3 h after MCAO. Lesion size was assessed at 3 and 6 h, and 1, 3, 4 and 7 days using MR imaging and histology. Functional outcome was assessed using the limb placement test and the treadmill stress test. Both hMSCs and PlGF-hMSCs reduced lesion volume, induced angiogenesis and elicited functional improvement compared with the control sham group, but the effect was greater in the PlGF-hMSC group. Enzyme-linked immunosorbent assay of the infarcted hemisphere revealed an increase in PlGF in both hMSC groups, but a greater increase in the PlGF-hMSC group. These data support the hypothesis that PlGF contributes to neuroprotection and angiogenesis in cerebral ischaemia, and cellular delivery of PlGF to the brain can be achieved by intravenous delivery of hMSCs.

Keywords: angiogenesis; bone marrow transplantation; neural transplantation; regeneration; stroke

Journal Article.  6936 words.  Illustrated.

Subjects: Neurology ; Neuroscience

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.