Adult Stem Cell Therapy and Heart Failure, 2000 to 2016

Abstract

Importance Stem cell therapy is a promising treatment strategy for patients with heart failure, which accounts for over 10% of deaths in the U.S. annually. Despite over a decade of research, further investigation is still needed to determine whether stem cell regenerative therapy is clinically effective and can be routinely implemented in clinical practice. Objective The purpose of this review is to describe the current progress in cardiac stem cell regenerative therapy using adult stem cells and highlight the merits and limitations of clinical trials performed to date. Evidence Review Information for this review was obtained through a search of PubMed and the Cochrane database for English language studies published between January 1, 2000 and April 20, 2016. Twenty-nine randomized clinical trials and 7 systematic reviews and meta-analyses were included in this review. Findings Although adult stem cells were once believed to have the ability to create new heart tissue or grow blood vessels, preclinical studies suggest instead that these cells release cardio-protective paracrine factors that activate endogenous pathways, leading to myocardial repair. Subsequent randomized controlled clinical trials, the majority of which used autologous bone marrow mononuclear cells, have found only a modest benefit in patients receiving stem cell therapy. The lack of a significant benefit may result from variations in trial methodology, discrepancies in reporting, and an over-reliance on surrogate endpoints. Conclusions and Relevance Although stem cell therapy for cardiovascular disease is not yet ready for routine clinical application, significant progress continues to be made. Physicians should be aware of the current status of this treatment so that they can better inform their patients who may be in search of alternative therapies.

Clinical Progress in Cell Therapy for Single Ventricle Congenital Heart Disease

“…5 We expect that cell therapy in children, however, will be much more successful. In fact, the young may be the best responders because their myocardium is inherently more pliable and will respond more vigorously to the biological cues of the transplanted cells.…”

Prolonged survival of transplanted stem cells after ischaemic injury via the slow release of pro-survival peptides from a collagen matrix

“…To identify pro-survival components for use in our biomaterial to treat ischaemic injury, we evaluated a selection of growth factors on the basis of previous studies from our laboratory and others (see Supplementary Table 1) 9–11 . For initial screening, bone marrow mononuclear cells (BMMNCs) were used, given their prevalence in clinical trials and their potential applications to human patients 12 . BMMNCs were harvested from transgenic L2G mice, which constitutively express the firefly luciferase (FLuc) and green fluorescence protein (GFP) reporter genes driven by the β-actin promoter, as previously described (Supplementary Fig.…”

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

“…Moreover, a growing number of phase I and II clinical trials have proven the feasibility and safety of SC application [381]. However, data from human studies addressing functional improvement are inconsistent.…”