Comparison of bone marrow stromal cells derived from stroke and normal rats for stroke treatment.
OBJECTIVE
We compared the effect of treatment of stroke with bone marrow stromal cells from stroke rats (Isch-BMSC) and normal rats (Nor-BMSC) on functional outcome.


METHODS
Isch-BMSCs and Nor-BMSCs were intravenously injected into rats 24 hours after middle cerebral artery occlusion. To test the mechanism of Isch-BMSC-enhanced neurorestoration, Isch-BMSC and Nor-BMSC cultures were used.


RESULTS
Isch-BMSC significantly promoted functional outcome and enhanced angiogenesis, arterial density, and axonal regeneration compared with Nor-BMSC treatment animals. Isch-BMSCs exhibited increased Angiopoietin-1, Tie2, basic fibroblast growth factor, glial cell-derived neurotrophic factor, vascular endothelial growth factor, and Flk1 gene expression compared with Nor-BMSC. Using transwell coculture of BMSCs with brain-derived endothelial cells, Isch-BMSCs increased phosphorylated-Tie2 activity in brain-derived endothelial cells and enhanced brain-derived endothelial cells capillary tube formation compared with Nor-BMSCs. Inhibition of Tie2 gene expression in brain-derived endothelial cells using siRNA significantly attenuated BMSC-induced capillary tube formation.


CONCLUSIONS
These data suggest that Isch-BMSCs are superior to Nor-BMSCs for the neurorestorative treatment of stroke, which may be mediated by the enhanced trophic factor and angiogenic characteristics of Isch-BMSCs.
Zacharek
Alex
A
Department of Neurology, Henry Ford Health Sciences Center, Detroit, Mich 48202, USA.
Shehadah
Amjad
A
Chen
Jieli
J
Cui
Xu
X
Roberts
Cynthia
C
Lu
Mei
M
Chopp
Michael
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002478:Cells, Cultured; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000473:pathology* / Q000601:surgery*; D017154:Stromal Cells / Q000637:transplantation; D016896:Treatment Outcome