Stem cell-derived exosomes in the treatment of acute myocardial infarction in preclinical animal models: a meta-analysis of randomized controlled trials

Abstract

Background: Exosomes (EXOs) derived from stem cells have become a potential new treatment for acute myocardial infarction (AMI). However, their impact is still not fully understood. Therefore, we performed this meta-analysis to systematically review the efficacy of EXOs on AMI in preclinical animal models.

Methods: We searched PubMed, EMBASE, and the Web of Science from September 1, 1980 to September 1, 2021, to retrieve the studies reporting the therapeutic effects of EXOs on AMI animal models. Secondary endpoints include the fractional shortening (FS), infarct size (IS), fibrosis area (FA), the TNF-α, IL-6 and IL-10 levels, the apoptosis rate and the number of autophagic vesicles. Two authors independently screened the articles based on inclusion and exclusion criteria. All statistical analyses were conducted using Stata14.0.

Results: Ten studies satisfied the inclusion criteria. Pooled analyses demonstrated that the levels of LVEF (WMD = 3.67%; 95% CI 2.28-5.07%; P = 0.000), FS (WMD = 3.69%; 95% CI 2.06-5.33%; P = 0.000), IS (WMD = -4.52%, 95% CI - 7.14 to - 1.9%; P = 0.001), and FA (WMD = -7.04%, 95% CI - 8.74 to - 5.34%; P = 0.000), TNF-α (WMD = -3.09, 95% CI - 5.47 to - 0.72; P = 0.011), TL-6 (WMD = -6.34, 95% CI - 11.2 to - 1.49; P < 0.01), TL-10 (WMD = 6.37, 95% CI 1.53-11.21; P = 0.01), the apoptosis rate (WMD = -8.23, 95% CI - 15.29 to - 1.17; P = 0.000), and the number of autophagic vesicles (WMD = -4.52, 95% CI - 7.43 to - 1.62; P = 0.000). Subgroup analysis showed that the EXOs were derived from HMSCs. Subgroup analysis showed that the EXOs derived from HMSCs, and that exosome therapy immediately after myocardial infarction can better improve the LVEF.

Conclusions: EXOs therapy has the potential to improve cardiac function, fibrogenesis, and inflammatory response, as well as reducing cell apoptosis and autophagy in preclinical AMI animal models. This can inform future human clinical trials of EXOs.

Keywords: Acute myocardial infarction; Animal models; Meta-analysis; Stem cell-derived exosomes.