Tissue-source Effect on Mesenchymal Stem Cells As Living Biodrugs for Heart Failure: Systematic Review and Meta-analysis

Background: Mesenchymal stem cells (MSCs), as living biodrugs, have entered advanced phases of clinical assessment for cardiac function restoration in patients with myocardial infarction and heart failure. While MSCs are available from diverse tissue sources, bone-marrow-derived MSCs (BM-MSCs) remain the most well-studied cell type, besides umbilical-cord-derived MSCs (UC-MSCs). The latter offers advantages, including noninvasive availability without ethical considerations.

Aim: To compare the safety and efficacy of BM-MSCs and UC-MSCs in terms of left ventricular ejection fraction (LVEF), 6-min walking distance (6MWD), and major adverse cardiac events (MACEs).

Methods: Five databases were systematically searched to identify randomized controlled trials (RCTs). Thirteen RCTs (693 patients) were included using predefined eligibility criteria. Weighted mean differences and odds ratio (OR) for the changes in the estimated treatment effects.

Results: UC-MSCs significantly improved LVEF controls by 5.08% [95% confidence interval (CI): 2.20%-7.95%] at 6 mo and 2.78% (95%CI: 0.86%-4.70%) at 12 mo. However, no significant effect was observed for BM-MSCs controls. No significant changes were observed in the 6MWD with either of the two cell types. Also, no differences were observed for MACEs, except rehospitalization rates, which were lower only with BM-MSCs (odds ratio 0.48, 95%CI: 0.24-0.97) controls.

Conclusion: UC-MSCs significantly improved LVEF compared with BM-MSCs. Their advantageous characteristics position them as a promising alternative to MSC-based therapy.