Angiogenesis in Rat Ischemic Hindlimb: Role of Human Bone Marrow-Derived Mesenchymal Stem Cells Transplantation
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- Category: Vol. 79, December 2011
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Angiogenesis in Rat Ischemic Hindlimb: Role of Human Bone Marrow-Derived Mesenchymal Stem Cells Transplantation,TAGHRID GAAFAR, HALA ALI, DINA SABRY, SOHAIR MAHFOUZ, HANAN A. MUBARAK and MAHITAB AHMED
Abstract
Background: The adult vasculature possesses the ability to remodel itself in response to a variety of stimuli, including hemodynamic forces (shear) and tissue metabolic demands (ischemia). This remodeling attempts to increase blood supply to better serve tissue metabolic demand. Better understanding of the mechanisms of vascular remodeling could lead to more effective treatments for these conditions.
Objectives: We postulated that human bone marrow de-rived-mesenchymal stem cells (hMSCs) delivery may give better prognosis in a rat model of unilateral peripheral vascular disease (unilateral femoral artery ligation).
Methods: Rat hindlimb ischemia model was established by surgical ligation the left femoral artery. Animals were divided into 3 groups; group I: Control sham-operated rats (n=15), group II: Ischemia group (n=15) that subjected to surgical left femoral artery ligation, group III: Ischemic with hMSCs group (n=15) that subjected to surgical left femoral artery ligation with IM injection of 5x 106 hMSCs. In vitro, hMSCs were isolated from human bone marrow aspiration and viability was measured by flow cytometry following culture. hMSCs were labeled by red fluorescent PKH dye for best cell tracing in vivo after cell transplantation. Muscle performance, peak isometric twitch force (Pt) and one half-relaxation time (1/2 RT), was assessed 4 weeks after surgery. After rat scarification, muscle tissues of the three studied groups were harvested for pathological assessment and for vascular endothelial growth factor (VEGF) gene expression using quantitative real time PCR.
Results: Ischemia with hMSCs group induced a significant improvement in blood reperfusion, detected by improved muscle performance, high significant level of VEGF gene expression and histopathological angiogenesis compared to ischemic group.
Conclusion: hMSCs transplantation would improve the functional angiogenesis and the contractile muscle performance in a rat model of hindlimb ischemia.