Cell-Free Treatments: A New Generation of Targeted Therapies for Treatment of Ischemic Heart Diseases

Although recent progress in medicine has substantially reduced cardiovascular diseases (CVDs)-related mortalities, current therapeutics have failed miserably to be beneficial for all patients with CVDs. A wide array of evidence suggests that newly-introduced cell-free treatments (CFTs) have more reliable results in the improvement of cardiac function. The main regeneration activity of CFTs protocols is based on bypassing cells and using paracrine factors. In this article, we aim to compare various stem cell secretomes, a part of a CFTs strategy, to generalize their effective clinical outcomes for patients with CVDs. Data for this review article were collected from 70 published articles (original, review, randomized clinical trials (RCTs), and case reports/series studies done on human and animals) obtained from Cochrane, Science Direct, PubMed, Scopus, Elsevier, and Google Scholar) from 2015 to April 2020 using six keywords. Full-text/full-length articles, abstract, section of book, chapter, and conference papers in English language were included. Studies with irrelevant/insufficient/data, or undefined practical methods were excluded. CFTs approaches involved in growth factors (GFs); gene-based therapies; microRNAs (miRNAs); extracellular vesicles (EVs) [exosomes (EXs) and microvesicles (MVs)]; and conditioned media (CM). EXs and CM have shown more remarkable results than stem cell therapy (SCT). GF-based therapies have useful results as well as side effects like pathologic angiogenesis. Cell source, cell′s aging and CM affect secretomes. Genetic manipulation of stem cells can change the secretome’s components. Growing progression to end stage heart failure (HF), propounds CFTs as an advantageous method with practical and clinical values for replacement of injured myocardium, and induction of neovascularization. To elucidate the secrets behind amplifying the expansion rate of cells, increasing life-expectancy, and improving quality of life (QOL) for patients with ischemic heart diseases (IHDs), collaboration among cell biologist, basic medical scientists, and cardiologists is highly recommended.