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Integrin ?1 Increases Stem Cell Survival and Cardiac Function after Myocardial Infarction.

ABSTRACT: Bone mesenchymal stem cells (BMSCs) transplantation is a promising therapeutic approach for myocardial infarction (MI), but its application is limited by poor viability of BMSCs. In this study, we aimed to improve the survival of BMSCs by lentivirus vector mediated overexpression of integrin ?1. In vitro study showed that integrin ?1 overexpression could facilitate the proliferation of BMSCs under oxygen glucose deprivation condition and regulated the expression of Caspase-3, Bax, Bcl-2, FAK, and ILK in BMSCs. Next, MI was induced in rat model and Igtb1BMSCs, NullBMSCs, or NatBMSCs were transplanted by intramyocardial injection. One week later, the survival of BMSCs was higher in Itgb1 BMSCs group than in other groups. Four weeks after transplantation, heart function was significantly improved in Igtb1BMSCs group compared to other groups. The expression levels of Caspase-3 and Bax were decreased while the expression levels of Bcl-2, FAK, ILK, and VEGF were increased in the cardiomyocytes of Igtb1BMSCs group compared to other groups. In conclusion, integrin ?1 overexpression could increase the survival of BMSCs and improve the efficacy of transplanted BMSCs for MI treatment. The beneficial effects may be mediated by inhibiting the apoptosis of both transplanted BMSCs and cardiomyocytes through adhesion-mediated cell survival signaling.

SUBMITTER: Li L

PROVIDER: S-EPMC5355448 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Integrin β1 Increases Stem Cell Survival and Cardiac Function after Myocardial Infarction.

Li Lili L Guan Qifan Q Dai Shuling S Wei Wen W Zhang Yao Y

Frontiers in pharmacology 20170317

Bone mesenchymal stem cells (BMSCs) transplantation is a promising therapeutic approach for myocardial infarction (MI), but its application is limited by poor viability of BMSCs. In this study, we aimed to improve the survival of BMSCs by lentivirus vector mediated overexpression of integrin β1. <i>In vitro</i> study showed that integrin β1 overexpression could facilitate the proliferation of BMSCs under oxygen glucose deprivation condition and regulated the expression of Caspase-3, Bax, Bcl-2, ...[more]

PMID: 28367125

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Project description:RATIONALE:Cortical bone stem cells (CBSCs) have been shown to reduce ventricular remodeling and improve cardiac function in a murine myocardial infarction (MI) model. These effects were superior to other stem cell types that have been used in recent early-stage clinical trials. However, CBSC efficacy has not been tested in a preclinical large animal model using approaches that could be applied to patients. OBJECTIVE:To determine whether post-MI transendocardial injection of allogeneic CBSCs reduces pathological structural and functional remodeling and prevents the development of heart failure in a swine MI model. METHODS AND RESULTS:Female Göttingen swine underwent left anterior descending coronary artery occlusion, followed by reperfusion (ischemia-reperfusion MI). Animals received, in a randomized, blinded manner, 1:1 ratio, CBSCs (n=9; 2×107 cells total) or placebo (vehicle; n=9) through NOGA-guided transendocardial injections. 5-ethynyl-2'deoxyuridine (EdU)-a thymidine analog-containing minipumps were inserted at the time of MI induction. At 72 hours (n=8), initial injury and cell retention were assessed. At 3 months post-MI, cardiac structure and function were evaluated by serial echocardiography and terminal invasive hemodynamics. CBSCs were present in the MI border zone and proliferating at 72 hours post-MI but had no effect on initial cardiac injury or structure. At 3 months, CBSC-treated hearts had significantly reduced scar size, smaller myocytes, and increased myocyte nuclear density. Noninvasive echocardiographic measurements showed that left ventricular volumes and ejection fraction were significantly more preserved in CBSC-treated hearts, and invasive hemodynamic measurements documented improved cardiac structure and functional reserve. The number of EdU+ cardiac myocytes was increased in CBSC- versus vehicle- treated animals. CONCLUSIONS:CBSC administration into the MI border zone reduces pathological cardiac structural and functional remodeling and improves left ventricular functional reserve. These effects reduce those processes that can lead to heart failure with reduced ejection fraction.

Dataset Information

Integrin ?1 Increases Stem Cell Survival and Cardiac Function after Myocardial Infarction.

Publications

Integrin β1 Increases Stem Cell Survival and Cardiac Function after Myocardial Infarction.

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