Therapeutic potential of human umbilical cord-derived stem cells in ischemic diseases.
ABSTRACT Recent advances suggest human umbilical cord is a new source for stem cells. Our laboratory has established a method to readily isolate and expand stem cells from human umbilical cord tissues. The aim of this study was to investigate the therapeutic potential of human umbilical cord-derived stem (UCDS) cells in ischemic diseases. The UCDS cells were characterized by flow cytometry and differentiation into osteogenic and adipogenic cells. Unilateral hind limb ischemia was surgically induced by femoral artery ligation in nude mice. The animals were intramuscularly injected with 10(6) UCDS cells or control phosphate-buffered saline. Blood perfusion of ischemic limbs was detected by laser Doppler perfusion imaging. Transplantation of UCDS cells to the ischemic limbs of nude mice significantly improved the blood flow to the affected limbs. Thus, transplantation of UCDS cells may potentially be a promising treatment for human ischemic diseases.
- SourceAvailable from: Cesar V Borlongan11/2011; , ISBN: 978-953-307-732-1
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ABSTRACT: Human umbilical cord multipotent mesenchymal stromal cells (UC-MSC) have recently been identified as ideal candidate stem cells for cell-based therapy. The present study was designed to evaluate therapeutic potentials of intracerebral administration of UC-MSC in a rat model of stroke. Rats were subjected to 2-hr middle cerebral artery occlusion and received 2 10 UC-MSC or phosphate-buffered saline as a control. Neurologic function evaluation was conducted weekly after transplantation. Brain injury volume and in vivo differentiation of transplanted UC-MSC were detected 2 or 5 weeks after the UC-MSC treatment. In addition, vascular density, vascular endothelial growth factor, and basic fibroblast growth factor expression in ipsilateral hemisphere after treatment and in vitro angiogenic potential of UC-MSC were assessed. The transplanted UC-MSC survived for at least 5 weeks in rat brain. Compared with the phosphate-buffered saline control, the UC-MSC treatment significantly reduced injury volume and neurologic functional deficits of rats after stroke. In ischemic brain, UC-MSC widely incorporated into cerebral vasculature and a subset of them was capable of differentiating into endothelial cells. Furthermore, the UC-MSC treatment substantially increased vascular density and vascular endothelial growth factor and basic fibroblast growth factor expression in ipsilateral hemisphere of stroke. In vitro induction and tube formation assay further confirmed their angiogenic properties. UC-MSC transplantation could accelerate neurologic functional recovery of rats after stroke, which may be mediated by their ability to promote angiogenesis.Transplantation 03/2009; 87(3):350-9. · 3.78 Impact Factor
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ABSTRACT: The objective of this study was to analyze the influence of TNF-α on rat mesenchymal stem cells (MSCs) and to assess feasibility of MSC transplantation to repair ischemic injury. In this study, adhesion molecules and cell specific surface markers on MSCs were measured after exposure to different concentrations of TNF-α. MSCs stimulated with varying concentrations of TNF-α were cultured with aortic endothelial cells, and the adhesion rate was measured. MSCs were then stimulated with an optimum concentration of TNF-α as determined in vitro, and injected intravenously into rats with ischemic hind limb injury. The number of MSCs in muscle samples from the ischemic area was counted. The results showed that (1) TNF-α induced a concentration-dependent increase in VCAM-1 expression in MSCs, whereas the expression of L-selectin, ICAM-1 and VLA-4 did not change significantly. Expression of MSC-specific antigens was unchanged. (2) MSCs pretreated with 10 ng/ml TNF-α showed significantly increased adhesion to endothelial cells in vitro, and accumulated to a greater extent in the areas of ischemic damage in rat hind limbs. We were able to conclude that TNF-α has no effect on expression of MSC-specific markers, but can increase the expression of VCAM-1 on rat MSCs. Suitable concentrations of TNF-α can promote MSC adhesion to endothelial cells and migration to damaged tissue.Cell biochemistry and biophysics 11/2011; 62(3):409-14. · 3.34 Impact Factor