Surfing the clinical trials of mesenchymal stem cell therapy in ischemic cardiomyopathy

Abstract

While existing remedies failed to fully address the consequences of heart failure, stem cell therapy has been introduced as a promising approach. The present review is a comprehensive appraisal of the impacts of using mesenchymal stem cells (MSCs) in clinical trials mainly conducted on ischemic cardiomyopathy. The benefits of MSC therapy for dysfunctional myocardium are likely attributed to numerous secreted paracrine factors and immunomodulatory effects. The positive outcomes associated with MSC therapy are scar size reduction, reverse remodeling, and angiogenesis. Also, a decreasing in the level of chronic inflammatory markers of heart failure progression like TNF-α is observed. The intense inflammatory reaction in the injured myocardial micro-environment predicts a poor response of scar tissue to MSC therapy. Subsequently, the interval delay between myocardial injury and MSC therapy is not yet determined. The optimal requested dose of cells ranges between 100 to 150 million cells. Allogenic MSCs have different advantages compared to autogenic cells and intra-myocardial injection is the preferred delivery route. The safety and efficacy of MSCs-based therapy have been confirmed in numerous studies, however several undefined parameters like route of administration, optimal timing, source of stem cells, and necessary dose are limiting the routine use of MSCs therapeutic approach in clinical practice. Lastly, pre-conditioning of MSCs and using of exosomes mediated MSCs or genetically modified MSCs may improve the overall therapeutic effect. Future prospective studies establishing a constant procedure for MSCs transplantation are required in order to apply MSC therapy in our daily clinical practice and subsequently improving the overall prognosis of ischemic heart failure patients.

HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction

“…MSCs may serve as therapeutic agents for ischemia-related diseases [ [21] , [22] , [23] , [24] ]. In the present study, human umbilical cord MSCs were used for cell culture and EVs isolation.…”

Allogeneic vs. autologous mesenchymal stem/stromal cells in their medication practice

“…As aforementioned, therapy with MSCs, autologous or allogeneic, improves left ventricular ejection fraction, decreases scar size, reverses ventricular remodeling along with eliciting the cell secretion of paracrine factors, although the exact mechanism of action of MSCs remains to be further investigated. However, therapeutic benefit is modest and there are frequently combined clinical results for MSC intervention in patients with ischemic cardiomyopathy [ 52 , 53 ]. Of note, the microenvironment in infarction heart may be harmful to transplanted MSC survival due to high concentration of free radicals [ 54 , 55 ].…”

Mass Customized Outlook for Regenerative Heart Failure Care

“…Pre-clinical work, as of today, has led to 793 registered clinical trials categorized under the keywords of “heart” and “cell therapy” at the U.S. National Library of Medicine database, ClinicalTrials.gov. This experience, based on over 1700 pre-clinical and clinical trials, has collectively enabled increasing levels of evidence with reassuring feasibility and safety for adult stem cell use [ 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. Indicators of benefit, however, have remained inconsistent among treated patients [ 44 , 45 ].…”