Abstract
Thrombolysis (rt-PA) is the only United States Food and Drug Administration (FDA) approved drug currently available. Unfortunately, its effect has been limited by the narrow therapeutic time window. Human cord blood mononuclear cells (cbMNC) is a promising treatment for ischemic stroke by forming collateral and neo-vascularization where it is one of the important factors that contribute to cell repair. Therefore, evaluation of neo-vascularization in sub-acute stroke may be beneficial for recovery. One group for healthy rat and three groups (n=6 per group) of male wistar rats have undergone permanent middle cerebral artery occlusion (MCAO). Transplantation 1x106 cells/kg of human cbMNC intra-arterially (IA) and intra-venously (IV) were administered after 7 days. Behavioural tests were performed before MCAO, 1 week after MCAO and at 3,9 and 14 days after cbMNC transplantation. Beta III tubulin protein (TUJ1), glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) antibody marker were evaluated. Spontaneous activity of transplanted rats by cbMNC have significantly improved compared to placebo group (p<0.05). Angiogenesis in IA group showed significant difference (P<0.001) when compared to IV and placebo respectively. The existence of neovascularization in the transplanted rats of cbMNC provide hope in accelerating repairment of the neuronal cells and functional outcome.
Highlights
Transplantation of human cord blood mononuclear cells (cbMNC) and their components (i.e., hematopoietic stem cells (HSCs), mesenchymal stem cell (MSCs), and endothelial progenitor cells (EPCs)) have been shown to be effective in animal models of ischemic stroke by decreasing apoptosis, inflamation in periinfarct area and stimulate angiogenesis, whether it was given by intra-arterially, intravenously nor intra-parenchymally[1]
One group for healthy rats and three groups (n=6 per group) of 250300 g of male wistar rats underwent permanent middle cerebral artery occlusion (MCAO) by using flame –blunted monofilament that already have been reported in our publication[10], where group 2 treated with physiological fluid intraarterially, group 3 treated with cbMNC intra-arterially and group 4 treated with cbMNC intra-venously
The presence of more neovascularization in the peri-infarct area provide hope that human cbMNC would stimulate the formation of collateral blood vessels by increasing the expression of vascular endothelial growth factor (VEGF) as an angiogenesis factor, it improves the functional outcome
Summary
Transplantation of human cbMNC and their components (i.e., hematopoietic stem cells (HSCs), mesenchymal stem cell (MSCs), and endothelial progenitor cells (EPCs)) have been shown to be effective in animal models of ischemic stroke by decreasing apoptosis, inflamation in periinfarct area and stimulate angiogenesis, whether it was given by intra-arterially, intravenously nor intra-parenchymally[1]. It has no doubt that during acute phase is the best time to save the cell neurons in penumbra area. It is reasonable when recanalization in acute phase occured will give more blood supply and minimalized the occuring of cell death. Since the collateral formations are important for outcome after stroke, understanding the effect of human cbMNC on angiogenesis and its potency for accelerating repairment of neuronal cells that would contribute to funcional outcome will give alternative therapy in the future. After recanalization, reperfusion with less complications may be achieved by intra-arterial human cbMNC transplantation[4]
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