VEGF improves survival of mesenchymal stem cells in infarcted hearts

Pons, Jennifer; Huang, Yu; Arakawa-Hoyt, Janice; Washko, Daniel; Takagawa, Junya; Ye, Jianqin; Grossman, William; Su, Hua

doi:10.1016/j.bbrc.2008.09.003

Cited by 122 publications

(81 citation statements)

References 22 publications

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“…The present results show significantly higher levels of VEGF in hypoxic-preconditioned cells. Since VEGF has also been shown to decrease apoptosis, delay senescence, and increase the expression of prosurvival factors, apart from its contributing role in angiogenesis (13,33), an increase in its expression would be crucial for the survival of the cells in the infarct cardiac tissue.…”

Section: Discussionmentioning

confidence: 99%

Hypoxic preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells

Chacko

Ahmed

Selvendiran

et al. 2010

American Journal of Physiology-Cell Physiology

173

114

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preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells. Am J Physiol Cell Physiol 299: C1562-C1570, 2010. First published September 22, 2010; doi:10.1152/ajpcell.00221.2010.-Stem cells transplanted to the ischemic myocardium usually encounter massive cell death within a few days of therapy. Hypoxic preconditioning (HPC) is currently employed as a strategy to prepare stem cells for increased survival and engraftment in the heart. However, HPC of stem cells has provided varying results, supposedly due to the differences in the oxygen concentration, duration of exposure, and passage conditions. In the present study, we determined the effect of HPC on rat mesenchymal stem cells (MSCs) exposed to 0.5% oxygen concentration for 24, 48, or 72 h. We evaluated the expression of prosurvival, proangiogenic, and functional markers such as hypoxia-inducible factor-1␣, VEGF, phosphorylated Akt, survivin, p21, cytochrome c, caspase-3, caspase-7, CXCR4, and c-Met. MSCs exposed to 24-h hypoxia showed reduced apoptosis on being subjected to severe hypoxic conditions. They also had significantly higher levels of prosurvival, proangiogenic, and prodifferentiation proteins when compared with longer exposure (72 h). Cells taken directly from the cryopreserved state did not respond effectively to the 24-h HPC as those that were cultured under normoxia before HPC. Cells cultured under normoxia before HPC showed decreased apoptosis, enhanced expression of connexin-43, cardiac myosin heavy chain, and CD31. The preconditioned cells were able to differentiate into the cardiovascular lineage. The results suggest that MSCs cultured under normoxia before 24-h HPC are in a state of optimal expression of prosurvival, proangiogenic, and functional proteins that may increase the survival and engraftment in the infarct heart. These results could provide further insights into optimal preparation of MSCs which would greatly influence the effectiveness of cell therapy in vivo. myocardial infarction; cell therapy THE OXYGEN CONCENTRATION in the microenvironment of stem cells plays an important role in controlling stem cell potency, proliferation, and differentiation ability (1,26,28). Stem cells that are normally cultured at ambient air in an in vitro environment differ in their exposure to the concentration of oxygen, compared with their natural physiological niches where they reside and function (7, 9). During cell transplantation procedures to treat conditions such as myocardial infarction (MI), the cultured stem cells encounter a sudden shortage in oxygen availability when transplanted into an ischemic heart tissue. A growing body of evidence attributes failure of stem cell therapy to the extensive loss of transplanted stem cells upon introducing them to such a harsh ischemic environment, which is high in inflammation factors and free radicals generated by oxidative stress (14, 38). Varying the oxygen exposure level while culturing the stem cells may play a major role in determining the survival of...

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Section: Discussionmentioning

confidence: 99%

Hypoxic preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells

Chacko

Ahmed

Selvendiran

et al. 2010

American Journal of Physiology-Cell Physiology

173

114

View full text Add to dashboard Cite

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“…Cardiac stem cells (CSCs) have been isolated from animal and human myocardium and are able to reconstitute the injured heart under experimental conditions (2,3,(11)(12)(13)(14)(15), suggesting the possibility of activation of endogenous repair mechanisms for myocardial regeneration. Several studies have demonstrated the use of growth factors and cytokines for endogenous stem cell stimulation through enhancement of mobilization, survival, proliferation, and differentiation (16)(17)(18)(19). Similarly, preconditioning of stem cells by genetic modification or priming with cytokines, growth factors, small molecules, and other pharmacological approaches, before transplantation, has significant effects on survival and engraftment (16,20,21).…”

mentioning

confidence: 99%

Agonists of growth hormone-releasing hormone stimulate self-renewal of cardiac stem cells and promote their survival

Florea

Majid

Kanashiro‐Takeuchi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The beneficial effects of agonists of growth hormone-releasing hormone receptor (GHRH-R) in heart failure models are associated with an increase in the number of ckit + cardiac stem cells (CSCs). The goal of the present study was to determine the presence of GHRH-R in CSCs, the effect of GHRH-R agonists on their proliferation and survival, and the mechanisms involved. We investigated the expression of GHRH-R in CSCs of different species and the effect of GHRH-R agonists on their cell proliferation and survival. GHRH-R is expressed in ckit + CSCs isolated from mouse, rat, and pig. Treatment of porcine CSCs with the GHRH-R agonist JI-38 significantly increased the rate of cell division. Similar results were observed with other GHRH-R agonists, MR-356 and MR-409. JI-38 exerted a protective effect on survival of porcine CSCs under conditions of oxidative stress induced by exposure to hydrogen peroxide. Treatment with JI-38 before exposure to peroxide significantly reduced cell death. A similar effect was observed with MR-356. Addition of GHRH-R agonists to porcine CSCs induced activation of ERK and AKT pathways as determined by increased expression of phospho-ERK and phospho-AKT. Inhibitors of ERK and AKT pathways completely reversed the effect of GHRH-R agonists on CSC proliferation. Our findings extend the observations of the expression of GHRH-R by CSCs and demonstrate that GHRH-R agonists have a direct effect on proliferation and survival of CSCs. These results support the therapeutic use of GHRH-R agonists for stimulating endogenous mechanisms for myocardial repair or for preconditioning of stem cells before transplantation.cardiac stem cells | growth hormone-releasing hormone | agonists | cell proliferation | cell survival

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“…They bring about changes in motility, proliferation, morphogenesis and survival. Various growth factors or cytokines, when added to culture medium, accelerate stem cells proliferation, including basic fibroblast growth factor (b-FGF), Platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) [26][27][28][29][30]. For example，PDGF could stimulate the MSCs proliferation rapidly and promote their secretion to form the extracellular matrix.…”

Section: Growth Factors or Cytokinesmentioning

confidence: 99%

Approaches for Stimulating Proliferation of Stem Cells in Vitro

Liu¹,

Li²,

Cai³

2017

JAMB

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Abstract.With the increasing incidence rates in the complex human diseases, e.g., Alzheimer's disease, spinal cord injury, and diabetes, there exists an urgent need to search for more effective and efficient therapies. Cell-based therapy has been considered to be a novel and effective therapeutic approach for the great potential of stem cells in their self-renewal and multipotential differentiational capacity. However, a major difficulty with the success of stem cell therapy is the availability of stem cells. The most serious issue is that only a limited number of stem cells can be extracted from adult tissue due to the decreasing frequency and differentiation potential with age. In order to achieve successful cell-based therapy, extensive ex vivo proliferation of stem cells is urgently required. Therefore, approaches to stimulate proliferation of stem cells are discussed in this article.

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VEGF improves survival of mesenchymal stem cells in infarcted hearts

Cited by 122 publications

References 22 publications

Hypoxic preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells

Hypoxic preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells

Agonists of growth hormone-releasing hormone stimulate self-renewal of cardiac stem cells and promote their survival

Approaches for Stimulating Proliferation of Stem Cells in Vitro

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