Cardiac Stem Cell Treatment in Myocardial Infarction

Abstract

Rationale: Cardiac stem cells (CSC) therapy has been clinically introduced for cardiac repair after myocardial infarction (MI). To date, there has been no systematic overview and meta-analysis of studies using CSC therapy for MI.Objective: Here, we used meta-analysis to establish the overall effect of CSCs in preclinical studies and assessed translational differences between and within large and small animals in the CSC therapy field. In addition, we explored the effect of CSC type and other clinically relevant parameters on functional outcome to better predict and design future (pre)clinical studies using CSCs for MI. Methods and Results:A systematic search was performed, yielding 80 studies. We determined the overall effect of CSC therapy on left ventricular ejection fraction and performed meta-regression to investigate clinically relevant parameters. We also assessed the quality of included studies and possible bias. The overall effect observed in CSC-treated animals was 10.7% (95% confidence interval 9.4-12.1; P<0.001) improvement in ejection fraction compared with placebo controls. Interestingly, CSC therapy had a greater effect in small animals compared with large animals (P<0.001). Meta-regression indicated that cell type was a significant predictor for ejection fraction improvement in small animals. Minor publication bias was observed in small animal studies. Conclusions:

Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction

“…A meta‐analysis of 10 cell therapy studies in large animal models reports a median injected dose (12×10 6  cells), which is similar to the doses used in our study 8. Our previous investigation in mice included a dose titration experiment showing that intramyocardial transplantation of 3×10 5 hAPCs is sufficient to achieve significant therapeutic effects 16.…”

Adult Stem Cell Therapy and Heart Failure, 2000 to 2016

“…36 The initial observation of improved ventricular function after AMI following BMMNC therapy led to the initiation of the BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial published in 2004, 37 which enrolled 60 patients randomized to receive intracoronary BMMNC therapy versus conventional medical therapy after percutaneous coronary intervention (PCI) for AMI. Although the study reported an improvement in left ventricular ejection fraction (LVEF) at 6 months following the BMMNC therapy, the observed benefit largely disappeared at 18 months except in those with significant infarct size (>60%) and depressed LVEF <50% at the time of therapy.…”

Cardiosphere-Derived Cells Require Endoglin for Paracrine-Mediated Angiogenesis

“…Furthermore, cardiac MRI was used to provide a robust readout of cardiac function, and investigators were blinded to treatments during the analysis. A recent systematic review of pre-clinical studies showed that the overall benefit of CDC and other cardiac stem cell treatments following MI was a small improvement in ejection fraction compared with placebo controls, but improvement was not present in all studies (Zwetsloot et al., 2016, Li et al., 2009). If improved functional outcomes are not reproducible in a standardized pre-clinical model, translation of any benefit to patients becomes even more challenging.…”