Harnessing the secretome of cardiac stem cells as therapy for ischemic heart disease

• Published in: Biochemical pharmacology Vol. 113; pp. 1 - 11
• Main Authors: Khanabdali, Ramin, Rosdah, Ayeshah A., Dusting, Gregory J., Lim, Shiang Y.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.08.2016
• Subjects: Adult Stem Cells - transplantation; Cardiac repair; Cardiac stem cells; Clinical Trials as Topic; Heart disease; Humans; Myocardial Ischemia - therapy; Myocytes, Cardiac - cytology; Neovascularization, Physiologic; Paracrine; Paracrine Communication - physiology; Protein therapy; Secretomes; Stem Cell Transplantation; Treatment Outcome; CDC; FSTL-1; PDGFR-α; Secretomes; SDF-1; Wt-1; CSC; ESC; Sca-1; Heart disease; TGF-β; CFU-F; MI; MSC; HGF; VEGF; iPSC; Cardiac stem cells; IGF-1; Cardiac repair; IL-1β; bFGF; ECM; MMP; TNF-α; Protein therapy; Paracrine; EPC; TIMP
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2016.02.012

Paracrine effects of cardiac stem cells can positively influence many processes in the infarcted myocardium, which in turn can lead to improvement of cardiac contractile function. [Display omitted] Adult stem cells continue to promise opportunities to repair damaged cardiac tissue. However, precisely how adult stem cells accomplish cardiac repair, especially after ischemic damage, remains controversial. It has been postulated that the clinical benefit of adult stem cells for cardiovascular disease results from the release of cytokines and growth factors by the transplanted cells. Studies in animal models of myocardial infarction have reported that such paracrine factors released from transplanted adult stem cells contribute to improved cardiac function by several processes. These include promoting neovascularization of damaged tissue, reducing inflammation, reducing fibrosis and scar formation, as well as protecting cardiomyocytes from apoptosis. In addition, these factors might also stimulate endogenous repair by activating cardiac stem cells. Interestingly, stem cells discovered to be resident in the heart appear to be functionally superior to extra-cardiac adult stem cells when transplanted for cardiac repair and regeneration. In this review, we discuss the therapeutic potential of cardiac stem cells and how the proteins secreted from these cells might be harnessed to promote repair and regeneration of damaged cardiac tissue. We also highlight how recent controversies about the efficacy of adult stem cells in clinical trials of ischemic heart disease have not dampened enthusiasm for the application of cardiac stem cells and their paracrine factors for cardiac repair: the latter have proved superior to the mesenchymal stem cells used in most clinical trials in the past, some of which appear to have been conducted with sub-optimal rigor.