Bone marrow mesenchymal stem cells transfer in patients with ST-segment elevation myocardial infarction: single-blind, randomized controlled muticentre trial

Abstract

Objective: Our aimed to evaluate efficacy and safety of intracoronary autologous bone morrow mesenchymal stem cells (BM-MSCs) transplantation in patients with ST-segment elevation myocardial infarction（STEMI）. Methods: In this randomised, single-blind, controlled trial, patients with STEMI (aged 39-76 years) were enrolled at 6 centers in Beijing (the People's Liberation Army Navy General Hospital, Beijing Armed Police General Hospital, Chinese People's Liberation Army General Hospital, Beijing Huaxin Hospital, Beijing Tongren Hospital, Beijing Chaoyang Hospital West Hospital). Patients underwent optimum medical treatment and percutaneous coronary intervention,and were randomly assigned in a 1:1 ratio to BM-MSCs group or control group. The primary endpoint was change of myocardial viability at 6 months' follow-up and left-ventricular (LV) function at 12 months' follow-up.The secondary endpoints were incidence of cardiovascular event, total mortality and adverse event at 12 months' follow-up. The myocardial viability assessed by single- photon emission tomography (SPECT). The left ventricular ejection fraction was used to assess LV function. All patients underwent dynamic ECG and laboratory evaluations. This trial is registered with ClinicalTrails.gov, number NCT04421274. Results: Between March , 2008, and July , 2010, 43 patients were randomly assigned to BM-MSCs group (n=21)or control group(n=22) and followed up for 12 months. LV ejection fraction increased from baseline to 12 months in the BM-MSCs group and control group ( mean baseline-adjusted BM-MSCs treatment differences in LV ejection fraction 4.8% (SD 9.0) and mean baseline-adjusted control group treatment differences in LV ejection fraction 5.8% (SD 6.04) ). After 6 months of follow-up, there was no significant improvement in myocardial metabolic activity in the BM-MSCs group before and after transplantation. however,there was no statistically significant difference between the two groups in the change of LV ejection fraction (p=0.30) and myocardial metabolic activity(p>0.05). We noticed that ,after 12 months of follow-up, except for 1 death and 1 coronary microvascular embolism in the BM-MSCs group, no other events occurred and Alanine transaminase(ALT) and C-reactive protein(CRP) in BM-MSCs group were significantly lower than that in control group. Conclusions: It is unreasonable to speculate that intracoronary transfer of autologous bone marrow MSCs could augment recovery of LV function and myocardial viability after acute myocardial infarction.Trial registration: clinicaltrials,NCT04421274. Registered 06,08,2020- Retrospectively registered, https://register.clinicaltrials.gov/NCT04421274.

Mesenchymal Stem Cell Transplantation in Patients With Acute Myocardial Infarction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…In this meta-analysis, we found that MSCs therapy within 2-14 days after PCI was more effective than MSCs transplantation within 2 days or 14 days after PCI. The results of present study also explain the negative results of our previous clinical trials [23]. The reason for the negative results of transplantation within 2 days after myocardial infarction may be due to the bad local microenvironment such as in ammation, which caused the death of a large number of transplanted cells, thereby affecting the transplantation effect.…”

“…The results of several clinical studies have shown that high-dose MSCs (10 8 cells) were more effective in improving LVEF [28,29]. In our previous clinical studies, the use of low cell doses (< 10 7 cells) did not nd signi cant improvement in cardiac function [23]. Our meta-analysis results indicate that the optimal therapeutic dose of MSCs cell therapy may be 10 7~1 0 8 cells.…”

“…Follow-up duration was from 3 to 24 months. MSC was infused into intracoronary (7 studies) [ [23], adipose tissue (1 study) [9], and umbilical cords (1 study) [10]. The main characteristics of each individual study are summarized in Table 1 and Table 2.…”

“…9] [10][19] [20] [21] [22] [23] and intravascular (2 studies)[24] [25] routes. Total injected cell doses ranged from <10 7 to >108 , and infusion time after PCI was between less than 2 days and 2 weeks later.…”