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

作者：Galvez Monton Carolina; Bragos Ramon; Soler Botija Carolina; Diaz Gumes Idoia; Prat Vidal Cristina; Crisostomo Veronica; Sanchez Margallo Francisco M; Llucia Valldeperas Aida; Bogonez Franco Paco; Perea Gil Isaac; Roura Santiago; Bayes Genis Antoni

来源：Stem Cells Translational Medicine, 2017, 6(2): 647-655.

DOI：10.5966/sctm.2016-0063

• Myocardial infarction
• Magnetic resonance imaging
• Bioimpedance
• Angiogenesis
• Progenitor cells

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. 20.48 +/- 0.07 per day; p = .002) and phase angle slope (-0.18 degrees +/- 0.24 degrees per day vs. -3.52 degrees +/- 0.84 degrees 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. 1.6 +/- 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.

• 出版日期2017-2