Noninvasive Assessment of an Engineered Bioactive Graft in Myocardial Infarction: Impact on Cardiac Function and Scar Healing

Stem Cells Transl Med. 2017 Feb;6(2):647-655. doi: 10.5966/sctm.2016-0063. Epub 2016 Sep 2.

Abstract

Cardiac tissue engineering, which combines cells and biomaterials, is promising for limiting the sequelae of myocardial infarction (MI). We assessed myocardial function and scar evolution after implanting an engineered bioactive impedance graft (EBIG) in a swine MI model. The EBIG comprises a scaffold of decellularized human pericardium, green fluorescent protein-labeled porcine adipose tissue-derived progenitor cells (pATPCs), and a customized-design electrical impedance spectroscopy (EIS) monitoring system. Cardiac function was evaluated noninvasively by using magnetic resonance imaging (MRI). Scar healing was evaluated by using the EIS system within the implanted graft. Additionally, infarct size, fibrosis, and inflammation were explored by histopathology. Upon sacrifice 1 month after the intervention, MRI detected a significant improvement in left ventricular ejection fraction (7.5% ± 4.9% vs. 1.4% ± 3.7%; p = .038) and stroke volume (11.5 ± 5.9 ml vs. 3 ± 4.5 ml; p = .019) in EBIG-treated animals. Noninvasive EIS data analysis showed differences in both impedance magnitude ratio (-0.02 ± 0.04 per day vs. -0.48 ± 0.07 per day; p = .002) and phase angle slope (-0.18° ± 0.24° per day vs. -3.52° ± 0.84° per day; p = .004) in EBIG compared with control animals. Moreover, in EBIG-treated animals, the infarct size was 48% smaller (3.4% ± 0.6% vs. 6.5% ± 1%; p = .015), less inflammation was found by means of CD25+ lymphocytes (0.65 ± 0.12 vs. 1.26 ± 0.2; p = .006), and a lower collagen I/III ratio was detected (0.49 ± 0.06 vs. 1.66 ± 0.5; p = .019). An EBIG composed of acellular pericardium refilled with pATPCs significantly reduced infarct size and improved cardiac function in a preclinical model of MI. Noninvasive EIS monitoring was useful for tracking differential scar healing in EBIG-treated animals, which was confirmed by less inflammation and altered collagen deposit. Stem Cells Translational Medicine 2017;6:647-655.

Keywords: Angiogenesis; Bioimpedance; Magnetic resonance imaging; Myocardial infarction; Progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Dielectric Spectroscopy
  • Disease Models, Animal
  • Humans
  • Magnetic Resonance Imaging
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / surgery*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Myocytes, Cardiac / transplantation*
  • Phenotype
  • Recovery of Function
  • Regeneration*
  • Stem Cell Transplantation / methods*
  • Stem Cells* / metabolism
  • Stroke Volume
  • Sus scrofa
  • Time Factors
  • Tissue Engineering / methods*
  • Tissue Scaffolds*
  • Ventricular Function, Left*
  • Ventricular Remodeling*