Systematic Reviews
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Mar 26, 2025; 17(3): 102067
Published online Mar 26, 2025. doi: 10.4252/wjsc.v17.i3.102067
Clinical experience with cryopreserved mesenchymal stem cells for cardiovascular applications: A systematic review
Moaz Safwan, Mariam Safwan Bourgleh, Khawaja Husnain Haider
Moaz Safwan, Mariam Safwan Bourgleh, Khawaja Husnain Haider, Department of Basic Sciences, Sulaiman Al Rajhi University, Al Bukairiyah 51941, AlQaseem, Saudi Arabia
Author contributions: Haider KH designed and produced the study and its methodology; Safwan M and Bourgleh MS performed database research and screened the extracted records against eligibility criteria, performed the data extraction and plotted and validated the extracted data, performed the quality assessment of the included trials, and conducted the statistical analysis; Safwan M and Haider KH drafted the first manuscript; Safwan M, Bourgleh MS, and Haider KH reviewed the final manuscript; and all the authors contributed to the final manuscript. All authors have read and agreed to the published version of the manuscript.
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Khawaja Husnain Haider, PhD, Professor, Department of Basic Sciences, Sulaiman Al Rajhi University, PO Box 777, Al Bukairiyah 51941, AlQaseem, Saudi Arabia. kh.haider@sr.edu.sa
Received: October 7, 2024
Revised: January 17, 2025
Accepted: February 24, 2025
Published online: March 26, 2025
Processing time: 164 Days and 14.8 Hours
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 (CryoMSCs) 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 CryoMSCs 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 CryoMSCs 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, CryoMSCs demonstrated a significant 2.11% improvement in left ventricular ejection fraction (LVEF) [WMD (95%CI) = 2.11 (0.66-3.56), P = 0.004, I2 = 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, I2 = 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 CryoMSCs vs the control group.

CONCLUSION

CryoMSCs are a promising option for heart failure patients, particularly considering the current treatment options for cardiovascular diseases. Our data suggest that CryoMSCs could be a viable alternative or complementary treatment to the current options, potentially improving patient outcomes.

Keywords: Cardiovascular; Cryopreservation; Heart; Mesenchymal stem cells; Umbilical cord stem cells; Randomized controlled trials; Stem cells

Core Tip: Our study yields significant findings that are crucial for regenerative medicine and cardiology. Our findings revealed that cryopreserved mesenchymal stem cells (CryoMSCs) treatment, compared to the control group, resulted in a 2.11% improvement in left ventricular ejection fraction during six months of follow-up, offering hope for potential future therapies. Left ventricular ejection fraction improvement was higher when using umbilical cord-derived mesenchymal stem cells or CryoMSCs with more than 80% post-thaw viability. The CryoMSCs treatment was safe, as there was no significant difference in the incidence of major cardiac adverse events compared to the control group. In addition, no significant effects on mortality and readmission were observed in the CryoMSCs group compared to the control group.