Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients

作     者：Muhammad Candragupta Jihwaprani Idris Sula Mohamed Ahmed Charbat Khawaja Husnain Haider 

作者机构：Basic SciencesSRCAl Bukayriyah 52736AlQaseemSaudi Arabia 

出 版 物：《World Journal of Cardiology》 (世界心脏病学杂志（英文版）（电子版）)

年 卷 期：2024年第16卷第6期

页      面：339-354页

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

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

摘      要：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 *** of delivery(RoD)remains one of the critical determinants of safety and *** 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 MSCbased therapy and determines the outcome of the *** To investigate the effect of RoD of MSCs on safety and efficacy in HF *** RCTs were retrieved from six *** 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 *** Twelve RCTs were ***,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),*** biochemical efficacy outcomes,only the IC subgroup showed a significant reduction in pro-