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• W2056331129 abstract "ObjectiveThis study evaluates usefulness of CXCR4 overexpression via retroviral transduction in adipose tissue−derived mesenchymal stem cells (AT-MSCs) as a strategy to increase their migration and engraftment ability.Materials and MethodsAT-MSCs were isolated from lipoaspirates from human healthy donors with liberase 3. Cells were transduced with retroviral vector carrying either CXCR4 or green fluorescent protein (GFP) complementary DNA, and neo-resistant colonies were selected and used in experiments. Chemotaxis, invasion through Matrigel, motor activity, gene expression, osteodifferentiation potential, and engraftment into bone marrow of nonobese diabetic/severe combined immunodeficient mice were analyzed for CXCR4-overexpressing cells and GFP-control cells.ResultsApproximately 90% of retrovirus-transduced AT-MSCs expressed CXCR4 or GFP and maintained their ability to differentiate into osteocytes. CXCR4-transduced AT-MSCs displayed enhanced migration and higher invasiveness toward SDF-1 gradient. The upregulation of CXCR4 led to phosphorylation of mitogen-activated protein and AKT kinases and an increase in metalloproteinase expression after SDF-1 stimulation. The transplantation of CXCR4-transduced AT-MSCs into nonobese diabetic/severe combined immunodeficient mice led to increased engraftment into bone marrow in comparison to GFP-transduced AT-MSCs.ConclusionsAdipose tissue is one of the alternative sources of MSCs to bone marrow. We showed that AT-MSCs overexpressing CXCR4 preserve their ability for osteodifferentiation. Enhanced migration and engraftment of the transduced AT-MSCs into bone marrow indicate the usefulness of this strategy in overcoming low engraftment of MSCs in clinical approaches of cellular therapies for bone disorders and can represent a powerful tool in regenerative medicine and gene therapies. Thus, these cells may be used as an alternative to bone marrow−derived MSCs. This study evaluates usefulness of CXCR4 overexpression via retroviral transduction in adipose tissue−derived mesenchymal stem cells (AT-MSCs) as a strategy to increase their migration and engraftment ability. AT-MSCs were isolated from lipoaspirates from human healthy donors with liberase 3. Cells were transduced with retroviral vector carrying either CXCR4 or green fluorescent protein (GFP) complementary DNA, and neo-resistant colonies were selected and used in experiments. Chemotaxis, invasion through Matrigel, motor activity, gene expression, osteodifferentiation potential, and engraftment into bone marrow of nonobese diabetic/severe combined immunodeficient mice were analyzed for CXCR4-overexpressing cells and GFP-control cells. Approximately 90% of retrovirus-transduced AT-MSCs expressed CXCR4 or GFP and maintained their ability to differentiate into osteocytes. CXCR4-transduced AT-MSCs displayed enhanced migration and higher invasiveness toward SDF-1 gradient. The upregulation of CXCR4 led to phosphorylation of mitogen-activated protein and AKT kinases and an increase in metalloproteinase expression after SDF-1 stimulation. The transplantation of CXCR4-transduced AT-MSCs into nonobese diabetic/severe combined immunodeficient mice led to increased engraftment into bone marrow in comparison to GFP-transduced AT-MSCs. Adipose tissue is one of the alternative sources of MSCs to bone marrow. We showed that AT-MSCs overexpressing CXCR4 preserve their ability for osteodifferentiation. Enhanced migration and engraftment of the transduced AT-MSCs into bone marrow indicate the usefulness of this strategy in overcoming low engraftment of MSCs in clinical approaches of cellular therapies for bone disorders and can represent a powerful tool in regenerative medicine and gene therapies. Thus, these cells may be used as an alternative to bone marrow−derived MSCs." @default.
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• W2056331129 date "2011-06-01" @default.
• W2056331129 modified "2023-10-17" @default.
• W2056331129 title "Genetically modified adipose tissue−derived mesenchymal stem cells overexpressing CXCR4 display increased motility, invasiveness, and homing to bone marrow of NOD/SCID mice" @default.
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• W2056331129 doi "https://doi.org/10.1016/j.exphem.2011.03.004" @default.
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