Stem Cell Therapy with Overexpressed VEGF and PDGF Genes Improves Cardiac Function in a Rat Infarct Model

Das, Hiranmoy; George, Jon C.; Joseph, Matthew; Das, Manjusri; Abdulhameed, Nasreen; Blitz, Anna; Khan, Mahmood; Sakthivel, R.; Mao, Hai‐Quan; Hoit, Brian D.; Kuppusamy, Periannan; Pompili, Vincent J.

doi:10.1371/journal.pone.0007325

Cited by 90 publications

(68 citation statements)

References 52 publications

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“…Also, compared with unmodified cells, MSCs transfected with VEGF exhibited significantly higher levels of myocardial angiogenesis and cardiomyocyte regeneration, and prevented progressive scar formation and heart dysfunction in a rodent model of myocardial ischaemia [55]. Consistently, our group has reported similar results in human cord bloodderived haematopoietic cells overexpressing VEGF and PDGF [42]. increased their viability in infarcted hearts, thus helping to attenuate cardiac fibrosis and preserve the contractile function, possibly through enhancing paracrine signalling from MSCs via anti-fibrotic factors such as HGF [56].…”

Section: Stem Cell Modifications and Cardiac Fibrosissupporting

confidence: 75%

Stem cell transplantation as a therapy for cardiac fibrosis

Elnakish

Kuppusamy

Khan

2012

The Journal of Pathology

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Cardiac fibrosis is a fundamental constituent of most cardiac pathologies and represents the upshot of nearly all types of cardiac injury. Generally, fibrosis is a scarring process, characterized by accumulation of fibroblasts and deposition of increasing amounts of extracellular matrix (ECM) proteins in the myocardium. Therapeutic approaches that control fibroblast activity and evade maladaptive processes could represent a potential strategy to attenuate progression towards heart failure. Currently, cell therapy is actively perceived as an alternative to traditional pharmacological management of myocardial infarction (MI). The majority of the studies applying stem cell therapy following MI have demonstrated a decline in fibrosis. However, it was not clearly recognized whether the decline in cardiac fibrosis was due to replacement of dead cardiomyocytes or because of the direct effects of paracrine factors released from the transplanted stem cells on the ECM. Therefore, the main focus of this review is to discuss the impact of different types of stem cells on cardiac fibrosis and associated cardiac remodelling in a variety of experimental models of heart failure, particularly MI.

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Section: Stem Cell Modifications and Cardiac Fibrosissupporting

confidence: 75%

Stem cell transplantation as a therapy for cardiac fibrosis

Elnakish

Kuppusamy

Khan

2012

The Journal of Pathology

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“…They have also been known to provide beneficial effects on the heart, including neovascularization [46,47] and attenuation of ventricular wall thinning [48]. Previous studies have attributed the angiogenic function of PRP to PDGF and VEGF [49], and the interaction between PDGF and PDGFR is key for the survival of many cells [50]. Specifically, PDGFR is reported to play pivotal roles by transducing extracellular stimuli to intracellular signaling circuits via the PDGF/ PDGFR axis to promote cellular growth and proliferation [51], as well as support pericyte/endothelial cell interplay and vasculature stability [52][53][54].…”

Section: Discussionmentioning

confidence: 99%

Platelet Rich Plasma Clot Releasate Preconditioning Induced PI3K/AKT/NFκB Signaling Enhances Survival and Regenerative Function of Rat Bone Marrow Mesenchymal Stem Cells in Hostile Microenvironments

Peng

Huang²,

Wu³

et al. 2013

Stem Cells and Development

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Mesenchymal stem cells (MSCs) have been optimal targets in the development of cell based therapies, but their limited availability and high death rate after transplantation remains a concern in clinical applications. This study describes novel effects of platelet rich clot releasate (PRCR) on rat bone marrow-derived MSCs (BM-MSCs), with the former driving a gene program, which can reduce apoptosis and promote the regenerative function of the latter in hostile microenvironments through enhancement of paracrine/autocrine factors. By using reverse transcriptionpolymerase chain reaction, immunofluorescence and western blot analyses, we showed that PRCR preconditioning could alleviate the apoptosis of BM-MSCs under stress conditions induced by hydrogen peroxide (H 2 O 2 ) and serum deprivation by enhancing expression of vascular endothelial growth factor and platelet-derived growth factor (PDGF) via stimulation of the platelet-derived growth factor receptor (PDGFR)/PI3K/AKT/NF-jB signaling pathways. Furthermore, the effects of PRCR preconditioned GFP-BM-MSCs subcutaneously transplanted into rats 6 h after wound surgery were examined by histological and other tests from days 0-22 after transplantation. Engraftment of the PRCR preconditioned BM-MSCs not only significantly attenuated apoptosis and wound size but also improved epithelization and blood vessel regeneration of skin via regulation of the wound microenvironment. Thus, preconditioning with PRCR, which reprograms BM-MSCs to tolerate hostile microenvironments and enhance regenerative function by increasing levels of paracrine factors through PDGFR-a/PI3K/AKT/NF-jB signaling pathways would be a safe method for boosting the effectiveness of transplantation therapy in the clinic.

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“…Participation of red BM cells in angiogenesis is related to secretion of angiogenic factors VEGF, bFGF, HGF, TGF-β, angiopoietin-1, etc. by these cells [6].…”

Section: Resultsmentioning

confidence: 95%

Reparation of the Myocardium after Transplantation of Mononuclear Bone Marrow Cells

et al. 2011

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Safety and efficiency of intracoronary transventricular transplantation of autologous mononuclear bone marrow cells in rats with postinfarction cardiosclerosis were studied. The cells migrated to the damaged area and were detected only in the cicatricial tissue; they have fibroblast-like phenotype and some of them were stained with Fapα (marker of reactive fibroblasts). More active proliferation of non-muscular cells and formation and maturation of collagen fibers in the cicatricial tissue were observed after transplantation of mononuclear cells. This led to thickening of the cicatricial wall, but the size of the scar and index of dilatation of the left ventricle remained unchanged. The number and volume density of newly formed blood vessels in the damaged area increased after transplantation, but no labeled cells were seen in the vascular walls. It can be hypothesized that stimulation of neoangiogenesis is mediated by paracrine mechanisms, which also explains improvement of global contractility of the left ventricle (increased contractility index in functional tests). Thus, transplantation of mononuclear bone marrow cells leads to thickening and strengthening of the cicatricial wall, stimulates angiogenesis, and improves global myocardial contractility. However, no morphological signs of reverse remodeling of the left-ventricular myocardium were revealed.

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Stem Cell Therapy with Overexpressed VEGF and PDGF Genes Improves Cardiac Function in a Rat Infarct Model

Cited by 90 publications

References 52 publications

Stem cell transplantation as a therapy for cardiac fibrosis

Stem cell transplantation as a therapy for cardiac fibrosis

Platelet Rich Plasma Clot Releasate Preconditioning Induced PI3K/AKT/NFκB Signaling Enhances Survival and Regenerative Function of Rat Bone Marrow Mesenchymal Stem Cells in Hostile Microenvironments

Reparation of the Myocardium after Transplantation of Mononuclear Bone Marrow Cells

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