Effect of the dose, timing, and route of administration of mesenchymal stem cells on their regenerative capacity after myocardial infarction: A systematic review

Abstract

Background The global rise in cases of acute myocardial infarction (AMI) poses a significant health challenge, which is why adult stem cells have gained great importance in recent years, due to their potential to promote the regeneration of the flowcardiac tissue, among which multipotent mesenchymal stromal cells (MSCs) stand out, thanks to their clinical usefulness. Objectives To evaluate the effect of the dose, timing, and route of administration of MSCs on their regenerative capacity after MI. Methods We searched for randomized clinical trials and experimental studies published up to April 25, 2024, in Medline (PubMed) and Scopus. Results Nine clinical studies were included in the qualitative assessment. The main routes of application were coronary, intramyocardially, epicardial topical and systemic venous perfusion, which could have clinical effectiveness with doses of 1x106 MSC/Kg,1 to 3 x 106, 4x106 and those greater than 0.5x106, respectively. The median number of viable cells administered was 2.4x106 (IQR: 1.6-2.4) in the PCI group versus 1.6x106 in the RCVI group (p=0.167). Median ex vivo retention was 2.55% in the RCVI group, 30 days after AMI, and 39.40% in the PCI group. At 4 and 12 months of follow-up, a better left ventricular end-to-end (LVEF) was observed in the group treated with ADSCs, at 4 (51.8% ±5.4% vs. 35.5% ±1.9%) and 8 weeks (52.1%± 3.4% versus 34.2% ±4.7%, p = 0.048). Conclusions The dosing, timing of administration, and routes of administration were important factors to assess the efficacy of the MSC.