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

Circ Res. 2017 May 26;120(11):1768-1775. doi: 10.1161/CIRCRESAHA.116.310374. Epub 2017 Mar 15.

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.

Keywords: artificial cells; mesenchymal stem cells; myocardial infarction; regeneration; stem cells; tissue engineering.

MeSH terms

  • Animals
  • Cells, Cultured
  • Humans
  • Lactic Acid / administration & dosage*
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction / diagnostic imaging*
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy*
  • Polyglycolic Acid / administration & dosage*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Positron-Emission Tomography / methods
  • Treatment Outcome

Substances

  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid