Efficacy and Safety of Stem Cell Therapy in Advanced Heart Failure Patients: A Systematic Review with a Meta-analysis of Recent Trials Between 2017 and 2019

Abstract

ObjectiveThe effects of stem cell therapy in patients with advanced heart failure is an ongoing debate. This study aimed to assess the effectiveness and safety of stem cell therapy plus the standard of care as compared to the placebo plus the standard of care in advanced heart failure patients.MethodsA comprehensive keyword search of PubMed between 2017 and 2019 was performed to extract trials conducted with stem cell therapy controlled with placebo in advanced heart failure. We included randomized controlled trials (RCTs) with data on safety and efficacy in patients with advanced heart failure after stem cell transplantation.ResultsSix RCTs, consisting of 569 patients, were selected. Three-hundred sixty-seven (367) out of 369 participants from the eligible four out of six RCTs were included for efficacy analysis, as we lost two patients from the final analysis due to early death. Five-hundred twenty-six (526) out of 527 participants from the eligible five out of six RCTs were included for safety analysis, as we lost one patient from the final analysis for not being able to receive the intervention. Stem cell transplantation significantly improved left ventricular ejection fraction (LVEF) by 4.58% (95% CI: 3.73-5.43%; p = 0.00001), improved left ventricular end-systolic volume (LVESV) by -5.18 ml (95% CI: -9.74 to -0.63 ml; p =0.03), and there was no difference in the risk of all-cause mortality (OR 0.97; 95% CI: 0.52 to 1.78%; p = 0.91). The above results correlate with the previous meta-analysis data conducted in 2016.ConclusionsThis meta-analysis provided the cumulative efficacy and safety results of stem cell transplantation in advanced heart failure based on recent RCTs. The above results suggest that stem cell therapy was associated with a moderate improvement in LVEF, and the safety analysis indicates no increased risk of mortality in patients with advanced heart failure. This meta-analysis recommends conducting more RCTs comparing stem cell transplantation and placebo with a larger patient population and longer follow-up.

Meta-Analysis of Percutaneous Endomyocardial Cell Therapy in Patients with Ischemic Heart Failure by Combination of Individual Patient Data (IPD) of ACCRUE and Publication-Based Aggregate Data

“…Supplementary Table S5 summarizes the results of previous publication-based meta-analyses of ischemic HF trials including cell therapy treatment. Overall, there is a large heterogeneity between the studies, which is mainly due to the inclusion of trials with different cell delivery routes and included patient populations [ 2 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ] Direct visual intramyocardial injection during open heart surgery is feasible and offers a relatively simple technology to deliver regenerative substances into the ischemic area, which is not treatable with bypass surgery. However, direct surgical intramyocardial cell delivery studies carry the ethical problems of a proper control group, or the combination of cell delivery and revascularization via aortocoronary bypass operation not enabling the sovereign cell effect.…”

Holistic Approach of Swiss Fetal Progenitor Cell Banking: Optimizing Safe and Sustainable Substrates for Regenerative Medicine and Biotechnology

“…Requirements for potential transformation and widespread therapeutic use comprise safety and consistency, availability in adequate quantities, traceable characterization, sufficient inherent expansion capacity, and compatibility with acceptable delivery methods such as engineered bioscaffolds (Doyle and Griffiths, 1998;Monti et al, 2012). Diverse classes of cell sources fit these restrictive criteria, including, but without being limited to, fetal progenitor cells (FPC), embryonic stem cells (ESC), adult stem cells [adipose stem cells (ASC), bone marrow-derived mesenchymal stem cells (BM-MSC), itMSC (ischemia-tolerant mesenchymal stem cells)], neural stem cells (NSC), limbal stem cells (LSC), hematopoietic stem cells (HSC), endothelial progenitor cells (EPC), umbilical cord cells, neonatal foreskin cells, platelets, placenta, and amniotic fluid cells (Vertelov et al, 2013;Heathman et al, 2015;Mount et al, 2015;Muraca et al, 2017;Li and Maitz, 2018;Sacchetti et al, 2018;Jayaraj et al, 2019;Torres-Torrillas et al, 2019). Most available cell sources are technically demanding, as progeny cells require dedicated processing or biochemical manipulation to orient or stabilize their potency and self-renewal capacity.…”

Stem cells for treatment of cardiovascular diseases: An umbrella review of randomized controlled trials

“…After removing the duplicates, we started our selection and evaluated 184 papers, with 52 assessed as full text. As reported in the PRISMA flow-chart (Figure 1), we identified 11 meta-analyses as eligible, with 34 outcomes (Fan et al, 2019;Fernandes et al, 2019;Jayaraj et al, 2019;Jeong et al, 2018;Jiang et al, 2016;Jones et al, 2019;Kuswardhani and Soejitno, 2011;Liu et al, 2015;Marquis-Gravel et al, 2014;Sun et al, 2015;Velagapudi et al, 2019).…”