Abstract
BACKGROUND: As living biodrugs, mesenchymal stem cells (MSCs) have progressed to phase 3 clinical trials for cardiovascular applications. However, their limited immediate availability hampers their routine clinical use. AIM: To validate our hypothesis that cryopreserved MSCs ((Cryo)MSCs) are as safe and effective as freshly cultured MSC counterparts but carry logistical advantages. METHODS: Four databases were systematically reviewed for relevant randomized controlled trials (RCTs) evaluating the safety and efficacy of (Cryo)MSCs from various tissue sources in treating patients with heart disease. A subgroup analysis was performed based on MSC source and post-thaw cell viability to determine treatment effects across different (Cryo)MSCs sources and viability status. Weighted mean differences (WMDs) and odds ratios were calculated to measure changes in the estimated treatment effects. All statistical analyses were performed using RevMan version 5.4.1 software. RESULTS: Seven RCTs (285 patients) met the eligibility criteria for inclusion in the meta-analysis. During short-term follow-up, (Cryo)MSCs demonstrated a significant 2.11% improvement in left ventricular ejection fraction (LVEF) [WMD (95%CI) = 2.11 (0.66-3.56), P = 0.004, I (2) = 1%], with umbilical cord-derived MSCs being the most effective cell type. However, the significant effect on LVEF was not sustained over the 12 months of follow-up. Subgroup analysis demonstrated a substantial 3.44% improvement in LVEF [WMD (95%CI) = 3.44 (1.46-5.43), P = 0.0007, I (2) = 0%] when using MSCs with post-thaw viability exceeding 80%. There was no statistically significant difference in the frequency of major cardiac adverse events observed in rehospitalization or mortality in patients treated with (Cryo)MSCs vs the control group. CONCLUSION: (Cryo)MSCs are a promising option for heart failure patients, particularly considering the current treatment options for cardiovascular diseases. Our data suggest that (Cryo)MSCs could be a viable alternative or complementary treatment to the current options, potentially improving patient outcomes.