Meta-Analysis
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Jun 26, 2024; 16(6): 339-354
Published online Jun 26, 2024. doi: 10.4330/wjc.v16.i6.339
Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients
Muhammad Candragupta Jihwaprani, Idris Sula, Mohamed Ahmed Charbat, Khawaja Husnain Haider
Muhammad Candragupta Jihwaprani, Idris Sula, Mohamed Ahmed Charbat, Khawaja Husnain Haider, Basic Sciences, SRC, Al Bukayriyah 52736, AlQaseem, Saudi Arabia
Author contributions: Haider KH designed and produced the study and its methodology; Jihwaprani MC and Sula I performed database research and screened the extracted records against eligibility criteria; Jihwaprani MC, Sula I, and Charbat MA performed data extraction and plotting; Sula I and Charbat MA reviewed and validated the extracted data; Jihwaprani MC, Sula I, and Charbat MA performed the quality assessment of the included trials; Jihwaprani MC, Sula I, and Charbat MA conducted the statistical analysis; Jihwaprani MC, Sula I, and Charbat MA drafted the first manuscript; Haider KH contributed to the final manuscript; Jihwaprani MC, Sula I, Charbat MA, and Haider KH reviewed the final manuscript; and all authors have read and agreed to the published version of the manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
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, BPharm, BSc, PhD, Chairman, Full Professor, Basic Sciences, SRC, AlMadina Road, Al Bukayriyah 52736, AlQaseem, Saudi Arabia. kh.haider@sr.edu.sa
Received: February 22, 2024
Revised: May 21, 2024
Accepted: May 24, 2024
Published online: June 26, 2024
Processing time: 123 Days and 14.4 Hours
Abstract
BACKGROUND

Mesenchymal stem cells (MSCs) as living biopharmaceuticals with unique properties, i.e., stemness, viability, phenotypes, paracrine activity, etc., need to be administered such that they reach the target site, maintaining these properties unchanged and are retained at the injury site to participate in the repair process. Route of delivery (RoD) remains one of the critical determinants of safety and efficacy. This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure (HF) based on phase II randomized clinical trials (RCTs). We hypothesize that the RoD modulates the safety and efficacy of MSC-based therapy and determines the outcome of the intervention.

AIM

To investigate the effect of RoD of MSCs on safety and efficacy in HF patients.

METHODS

RCTs were retrieved from six databases. Safety endpoints included mortality and serious adverse events (SAEs), while efficacy outcomes encompassed changes in left ventricular ejection fraction (LVEF), 6-minute walk distance (6MWD), and pro-B-type natriuretic peptide (pro-BNP). Subgroup analyses on RoD were performed for all study endpoints.

RESULTS

Twelve RCTs were included. Overall, MSC therapy demonstrated a significant decrease in mortality [relative risk (RR): 0.55, 95% confidence interval (95%CI): 0.33-0.92, P = 0.02] compared to control, while SAE outcomes showed no significant difference (RR: 0.84, 95%CI: 0.66-1.05, P = 0.11). RoD subgroup analysis revealed a significant difference in SAE among the transendocardial (TESI) injection subgroup (RR = 0.71, 95%CI: 0.54-0.95, P = 0.04). The pooled weighted mean difference (WMD) demonstrated an overall significant improvement of LVEF by 2.44% (WMD: 2.44%, 95%CI: 0.80-4.29, P value ≤ 0.001), with only intracoronary (IC) subgroup showing significant improvement (WMD: 7.26%, 95%CI: 5.61-8.92, P ≤ 0.001). Furthermore, the IC delivery route significantly improved 6MWD by 115 m (WMD = 114.99 m, 95%CI: 91.48-138.50), respectively. In biochemical efficacy outcomes, only the IC subgroup showed a significant reduction in pro-BNP by -860.64 pg/mL (WMD: -860.64 pg/Ml, 95%CI: -944.02 to -777.26, P = 0.001).

CONCLUSION

Our study concluded that all delivery methods of MSC-based therapy are safe. Despite the overall benefits in efficacy, the TESI and IC routes provided better outcomes than other methods. Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.

Keywords: Clinical trial; Heart failure; Mesenchymal stem cells; Living biodrug; Meta-analysis; Stem cells; Systematic review

Core Tip: Route of delivery (RoD) remains a critical determinant of safety and efficacy in cardiac stem cell therapy, particularly in heart failure (HF) patients. HF occurs when the heart’s pumping ability is inadequate to meet the body’s metabolic needs. Mesenchymal stem cells (MSCs) are living biopharmaceuticals with unique properties that need to be administered such that they reach the target site and are retained there to participate in the repair process. This systematic review and meta-analysis of phase II randomized clinical trials determine the RoD effect on the safety and efficacy of MSCs during HF treatment.