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.

In Situ-Crosslinked Zippersomes Enhance Cardiac Repair by Increasing Accumulation and Retention

“…MSC-derived EVs have been used as a promising alternative to live cell therapies for the treatment of MI and wound healing [40][41][42][43][44] . Many studies have now shown that EVs are key mediators of stem cell-mediated wound healing and regeneration within the damaged heart, largely due to their ability to move, even through occluded sites.…”

Customized Loading of microRNA-126 to Small Extracellular Vesicle-Derived Vehicles Improves Cardiac Function after Myocardial Infarction

“…To recapitulate this rapid clinical response in the in vivo setting, there is value to administering the in vivo therapies right after the onset of IR. Moreover, a meta-analysis of 10 sEV therapies for acute MI in small animal models shows that most sEV therapies are delivered between 0 and 60 min after the IR . Based on these prior studies, to increase the clinical relevance of our work and for ease of intramyocardial injection while the chest cavity is opened, we chose to deliver our CPC sEVs and ELVs immediately after IR.…”

“…However, a limitation of these current sEV studies is the extent of the improvements. The in vivo therapeutic benefit results in only a roughly 3% increase in echocardiographic parameters . In addition, the reparative capacity of the sEVs is cell dependent and varies based on CPC conditions such as microenvironmental oxygen levels and parent cell age. , Specifically, sEVs derived from younger CPCs and under hypoxic conditions have been more reparative.…”

Causal effects for genetic variants of osteoprotegerin on the risk of acute myocardial infarction and coronary heart disease: A two-sample Mendelian randomization study

“…Secondly, rs1385492 is related to TNF by consulting the GWAS catalog. It is well known that TNF plays a crucial important role in causing and developing the disease in cardiovascular medicine ( 36 – 38 ).…”