Fabrication of Synthetic Mesenchymal Stem Cells for the Treatment of Acute Myocardial Infarction in Mice

TLDR

Stem cell therapy is limited by challenges in growth, preservation, and transport, prompting exploration of synthetic analogs that could overcome these hurdles. The study aims to fabricate synthetic mesenchymal stem cell analogs and evaluate their therapeutic efficacy in a mouse model of acute myocardial infarction. Researchers encapsulated MSC‑secreted factors in PLGA microparticles, coated them with MSC membranes, creating synthetic MSC (synMSC) particles. SynMSC displayed MSC‑like factor release and surface antigens, improved cardiomyocyte function, remained stable after cryopreservation and lyophilization, and when injected into infarcted mice, promoted angiogenesis and reduced left‑ventricular remodeling, demonstrating regenerative potential.

Abstract

Rationale: Stem cell therapy faces several challenges. It is difficult to grow, preserve, and transport stem cells before they are administered to the patient. Synthetic analogs for stem cells represent a new approach to overcome these hurdles and hold the potential to revolutionize regenerative medicine. Objective: We aim to fabricate synthetic analogs of stem cells and test their therapeutic potential for treatment of acute myocardial infarction in mice. Methods and Results: We packaged secreted factors from human bone marrow–derived mesenchymal stem cells (MSC) into poly(lactic-co-glycolic acid) microparticles and then coated them with MSC membranes. We named these therapeutic particles synthetic MSC (or synMSC). synMSC exhibited a factor release profile and surface antigens similar to those of genuine MSC. synMSC promoted cardiomyocyte functions and displayed cryopreservation and lyophilization stability in vitro and in vivo. In a mouse model of acute myocardial infarction, direct injection of synMSC promoted angiogenesis and mitigated left ventricle remodeling. Conclusions: We successfully fabricated a synMSC therapeutic particle and demonstrated its regenerative potential in mice with acute myocardial infarction. The synMSC strategy may provide novel insight into tissue engineering for treating multiple diseases.