Dataset Information

Transplantation of Rat Mesenchymal Stem Cells Overexpressing Hypoxia-Inducible Factor 2? Improves Blood Perfusion and Arteriogenesis in a Rat Hindlimb Ischemia Model.

ABSTRACT: Mesenchymal stem cells (MSCs) have been increasingly tested in cell-based therapy to treat numerous diseases. Genetic modification to improve MSC behavior may enhance posttransplantation outcome. This study aims to test the potential therapeutic benefits of rat bone marrow MSCs overexpressing hypoxia-inducible factor 2? (rMSCsHIF-2? ) in a rat hindlimb ischemia model. PBS, rMSCs, or rMSCsHIF-2? were injected into rat ischemic hindlimb. Compared with the injection of PBS or rMSCs, transplantation of rMSCsHIF-2? significantly improved blood perfusion, increased the number of vessel branches in the muscle of the ischemic hindlimb, and improved the foot mobility of the ischemic hindlimb (all P < 0.05). rMSCHIF-2? transplantation also markedly increased the expression of proangiogenic factors VEGF, bFGF, and SDF1 and Notch signaling proteins including DII4, NICD, Hey1, and Hes1, whereas it reduced the expression of proapoptotic factor Bax in the muscle of the ischemic hindlimb. Overexpression of HIF-2? did not affect rMSC stemness and proliferation under normoxia but significantly increased rMSC migration and tube formation in matrigel under hypoxia (all P < 0.05). RMSCsHIF-2? stimulated endothelial cell invasion under hypoxia significantly (P < 0.05). Genetic modification of rMSCs via overexpression of HIF-2? improves posttransplantation outcomes in a rat hindlimb ischemia model possibly by stimulating proangiogenic growth factors and cytokines.

SUBMITTER: Lu W

PROVIDER: S-EPMC5697133 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Transplantation of Rat Mesenchymal Stem Cells Overexpressing Hypoxia-Inducible Factor 2α Improves Blood Perfusion and Arteriogenesis in a Rat Hindlimb Ischemia Model.

Lu Weifeng W Chen Xiaoli X Si Yi Y Hong Shichai S Shi Zhengyu Z Fu Weiguo W

Stem cells international 20171107

Mesenchymal stem cells (MSCs) have been increasingly tested in cell-based therapy to treat numerous diseases. Genetic modification to improve MSC behavior may enhance posttransplantation outcome. This study aims to test the potential therapeutic benefits of rat bone marrow MSCs overexpressing hypoxia-inducible factor 2α (rMSCsHIF-2α ) in a rat hindlimb ischemia model. PBS, rMSCs, or rMSCsHIF-2α were injected into rat ischemic hindlimb. Compared with the ...[more]

PMID: 29238372

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Project description:ObjectiveThis study aimed to examine acellular extracellular matrix based hydrogels as potential therapies for treating peripheral artery disease (PAD). We tested the efficacy of using a tissue specific injectable hydrogel, derived from decellularized porcine skeletal muscle (SKM), compared to a new human umbilical cord derived matrix (hUC) hydrogel, which could have greater potential for tissue regeneration because of its young tissue source age.BackgroundThe prevalence of PAD is increasing and can lead to critical limb ischemia (CLI) with potential limb amputation. Currently there are no therapies for PAD that effectively treat all of the underlying pathologies, including reduced tissue perfusion and muscle atrophy.MethodsIn a rodent hindlimb ischemia model both hydrogels were injected 1-week post-surgery and perfusion was regularly monitored with laser speckle contrast analysis (LASCA) to 35 days post-injection. Histology and immunohistochemistry were used to assess neovascularization and muscle health. Whole transcriptome analysis was further conducted on SKM injected animals on 3 and 10 days post-injection.ResultsSignificant improvements in hindlimb tissue perfusion and perfusion kinetics were observed with both biomaterials. End point histology indicated this was a result of arteriogenesis, rather than angiogenesis, and that the materials were biocompatible. Skeletal muscle fiber morphology analysis indicated that the muscle treated with the tissue specific, SKM hydrogel more closely matched healthy tissue morphology. Short term histology also indicated arteriogenesis rather than angiogenesis, as well as improved recruitment of skeletal muscle progenitors. Whole transcriptome analysis indicated that the SKM hydrogel caused a shift in the inflammatory response, decreased cell death, and increased blood vessel and muscle development.ConclusionThese results show the efficacy of an injectable ECM hydrogel alone as a potential therapy for treating patients with PAD. Our results indicate that the SKM hydrogel improved functional outcomes through stimulation of arteriogenesis and muscle progenitor cell recruitment.

Dataset Information

Transplantation of Rat Mesenchymal Stem Cells Overexpressing Hypoxia-Inducible Factor 2? Improves Blood Perfusion and Arteriogenesis in a Rat Hindlimb Ischemia Model.

Publications

Transplantation of Rat Mesenchymal Stem Cells Overexpressing Hypoxia-Inducible Factor 2<i>α</i> Improves Blood Perfusion and Arteriogenesis in a Rat Hindlimb Ischemia Model.

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