Enhanced engraftment and repairing ability of human adipose-derived stem cells, conveyed by pharmacologically active microcarriers continuously releasing HGF and IGF-1, in healing myocardial infarction in rats

J Biomed Mater Res A. 2015 Sep;103(9):3012-25. doi: 10.1002/jbm.a.35442. Epub 2015 Mar 11.


One of the main cause of ineffective cell therapy in repairing the damaged heart is the poor yield of grafted cells. To overcome this drawback, rats with 4-week-old myocardial infarction (MI) were injected in the border zone with human adipose-derived stem cells (ADSCs) conveyed by poly(lactic-co-glycolic acid) microcarriers (PAMs) releasing hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) (GFsPAMs). According to treatments, animals were subdivided into different groups: MI_ADSC, MI_ADSC/PAM, MI_GFsPAM, MI_ADSC/GFsPAM, and untreated MI_V. Two weeks after injection, a 31% increase in ADSC engraftment was observed in MI_ADSC/PAM compared with MI_ADSC (p < 0.05). A further ADSC retention was obtained in MI_ADSC/GFsPAM with respect to MI_ADSC (106%, p < 0.05) and MI_ADSC/PAM (57%, p < 0.05). A 130% higher density of blood vessels of medium size was present in MI_ADSC/GFsPAM compared with MI_ADSC (p < 0.01). MI_ADSC/GFsPAM also improved, albeit slightly, left ventricular remodeling and hemodynamics with respect to the other groups. Notably, ADSCs and/or PAMs, with or without HGF/IGF-1, trended to induce arrhythmias in electrically driven, Langendorff-perfused, hearts of all groups. Thus, PAMs releasing HGF/IGF-1 markedly increase ADSC engraftment 2 weeks after injection and stimulate healing in chronically infarcted myocardium, but attention should be paid to potentially negative electrophysiological consequences.

Keywords: adipose-derived stem cell; arrhythmia; hepatocyte growth factor; insulin-like growth factor 1; myocardial infarction; pharmacologically active microcarrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Arrhythmias, Cardiac / etiology
  • Biomimetic Materials / chemistry
  • Disease Models, Animal
  • Drug Carriers / administration & dosage
  • Hepatocyte Growth Factor / administration & dosage*
  • Humans
  • Insulin-Like Growth Factor I / administration & dosage*
  • Lactic Acid
  • Male
  • Materials Testing
  • Microspheres
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • Neovascularization, Physiologic / drug effects
  • Polyglycolic Acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Rats, Wistar
  • Stem Cell Transplantation / adverse effects
  • Stem Cell Transplantation / methods*
  • Ventricular Remodeling
  • Wound Healing / drug effects


  • Drug Carriers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Hepatocyte Growth Factor
  • Insulin-Like Growth Factor I