Mesenchymal stem cells stimulate protective genetic reprogramming of injured cardiac ventricular myocytes

Rogers, Terry B.; Pati, Shibani; Gaa, Shirley; Riley, Dushon DeVere; Khakoo, Aarif Y.; Patel, Shalin; Wardlow, Robert D.; Frederick, Cecilia A.; Hall, Gentzon; He, Liu; Lederer, W. Jonathan

doi:10.1016/j.yjmcc.2010.09.001

Cited by 33 publications

(27 citation statements)

References 40 publications

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“…Human MSCs in coculture with neonatal mouse ventricular cardiac myocytes (nMCMs), injured by incubation with endotoxin or IL-1␤, protected cardiomyocyte calcium handling. Importantly, the presence of a semi-permeable membrane in this study suggested that paracrine signaling was operable (309).…”

Section: A Paracrine Effectsmentioning

confidence: 69%

Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue

Golpanian

Wolf

Hatzistergos

et al. 2016

Physiological Reviews

257

211

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Mesenchymal stem cells (MSCs) are broadly distributed cells that retain postnatal capacity for self-renewal and multilineage differentiation. MSCs evade immune detection, secrete an array of anti-inflammatory and anti-fibrotic mediators, and very importantly activate resident precursors. These properties form the basis for the strategy of clinical application of cell-based therapeutics for inflammatory and fibrotic conditions. In cardiovascular medicine, administration of autologous or allogeneic MSCs in patients with ischemic and nonischemic cardiomyopathy holds significant promise. Numerous preclinical studies of ischemic and nonischemic cardiomyopathy employing MSC-based therapy have demonstrated that the properties of reducing fibrosis, stimulating angiogenesis, and cardiomyogenesis have led to improvements in the structure and function of remodeled ventricles. Further attempts have been made to augment MSCs' effects through genetic modification and cell preconditioning. Progression of MSC therapy to early clinical trials has supported their role in improving cardiac structure and function, functional capacity, and patient quality of life. Emerging data have supported larger clinical trials that have been either completed or are currently underway. Mechanistically, MSC therapy is thought to benefit the heart by stimulating innate anti-fibrotic and regenerative responses. The mechanisms of action involve paracrine signaling, cell-cell interactions, and fusion with resident cells. Trans-differentiation of MSCs to bona fide cardiomyocytes and coronary vessels is also thought to occur, although at a nonphysiological level. Recently, MSC-based tissue engineering for cardiovascular disease has been examined with quite encouraging results. This review discusses MSCs from their basic biological characteristics to their role as a promising therapeutic strategy for clinical cardiovascular disease.

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Section: A Paracrine Effectsmentioning

confidence: 69%

Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue

Golpanian

Wolf

Hatzistergos

et al. 2016

Physiological Reviews

257

211

View full text Add to dashboard Cite

show abstract

“…Another explanation was that a paracrine function of stem cells and other cells could induce remodeling and cell protection, as well as improved function and facilitate cell transformation to cardiomyocytes. [105][106][107][108] Recent findings suggest that a surprisingly high number of different miRs can independently trigger cardiomyocyte mitosis in the border zone of an infarction, emphasizing the superiority of exosomal miRs over stem cell implantation in restitution of infarcted myocardium. This opens up for a new treatment strategy replacing stem cell implantation.…”

Section: Cardiac Remodeling and Exosome Functionmentioning

confidence: 99%

Role of Exosomes in Myocardial Remodeling

Waldenström

Ronquist

2014

Circulation Research

132

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“…Rehman et al 77 showed that adipose derived stem cells secrete angiogenic and antiapoptotic factors providing further evidence of cardioprotection. The responsible pathways may include activation of inflammation and stress response associated signaling pathways mediated by IGF-1 and inhibition of transcription factor NF-kB 78 . The cardioprotective effect was further enhanced by preconditioning the MSCs with TGF-β or by activating the TNF receptor-2 61 .…”

Section: Introductionmentioning

confidence: 99%

Use of Mesenchymal Stem Cells for Therapy of Cardiac Disease

Karantalis

Hare

2015

Circulation Research

357

332

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Despite substantial clinical advances over the past 65 years, cardiovascular disease remains the leading cause of death in America. The past 15 years has witnessed major basic and translational interest in the use of stem and/or precursor cells as a therapeutic agent for chronically injured organs. Among the cell types under investigation, adult mesenchymal stem cells (MSCs) are widely studied and in early stage clinical studies show promise for repair and regeneration of cardiac tissues. The ability of MSCs to differentiate into mesoderm and non-mesoderm derived tissues, their immunomodulatory effects, their availability and their key role in maintaining and replenishing endogenous stem cell niches have rendered them one of the most heavily investigated and clinically tested type of stem cell. Accumulating data from preclinical and early phase clinical trials document their safety when delivered as either autologous or allogeneic forms in a range of cardiovascular diseases, but also importantly define parameters of clinical efficacy that justify further investigation in larger clinical trials. Here, we review the biology of MSCs, their interaction with endogenous molecular and cellular pathways, and their modulation of immune responses. Additionally, we discuss factors that enhance their proliferative and regenerative ability and factors that may hinder their effectiveness in the clinical setting.

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Mesenchymal stem cells stimulate protective genetic reprogramming of injured cardiac ventricular myocytes

Cited by 33 publications

References 40 publications

Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue

Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue

Role of Exosomes in Myocardial Remodeling

Use of Mesenchymal Stem Cells for Therapy of Cardiac Disease

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