Noriyuki Kashiyama1, Robert L Kormos2, Yasumoto Matsumura3, Antonio D'Amore4, Shigeru Miyagawa5, Yoshiki Sawa5, William R Wagner6. 1. McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa; Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa; Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita-city, Osaka, Japan. 2. McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa; Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa. 3. McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa. 4. McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Fondazione RiMED, Palermo, Italy. 5. Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita-city, Osaka, Japan. 6. McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; Department of Surgery, University of Pittsburgh, Pittsburgh, Pa. Electronic address: wagnerwr@upmc.edu.
Abstract
OBJECTIVES: Although adipose-derived stem cells (ADSCs) have shown promise in cardiac regeneration, stable engraftment is still challenging. Acellular bioengineered cardiac patches have shown promise in positively altering ventricular remodeling in ischemic cardiomyopathy. We hypothesized that combining an ADSC sheet approach with a bioengineered patch would enhance ADSC engraftment and positively promote cardiac function compared with either therapy alone in a rat ischemic cardiomyopathy model. METHODS: Cardiac patches were generated from poly(ester carbonate urethane) urea and porcine decellularized cardiac extracellular matrix. ADSCs constitutively expressing green fluorescent protein were established from F344 rats and transplanted as a cell sheet over the left ventricle 3 days after left anterior descending artery ligation with or without an overlying cardiac patch. Cardiac function was serially evaluated using echocardiography for 8 weeks, comparing groups with combined cells and patch (group C, n = 9), ADSCs alone (group A, n = 7), patch alone (group P, n = 6) or sham groups (n = 7). RESULTS: Much greater numbers of ADSCs survived in the C versus A groups (P < .01). At 8 weeks posttransplant, the percentage fibrotic area was lower (P < .01) in groups C and P compared with the other groups and vasculature in the peri-infarct zone was greater in group C versus other groups (P < .01), and hepatocyte growth factor expression was higher in group C than in other groups (P < .05). Left ventricular ejection fraction was higher in group C versus other groups. CONCLUSIONS: A biodegradable cardiac patch enhanced ADSC engraftment, which was associated with greater cardiac function and neovascularization in the peri-infarct zone following subacute myocardial infarction. Published by Elsevier Inc.
OBJECTIVES: Although adipose-derived stem cells (ADSCs) have shown promise in cardiac regeneration, stable engraftment is still challenging. Acellular bioengineered cardiac patches have shown promise in positively altering ventricular remodeling in ischemic cardiomyopathy. We hypothesized that combining an ADSC sheet approach with a bioengineered patch would enhance ADSC engraftment and positively promote cardiac function compared with either therapy alone in a rat ischemic cardiomyopathy model. METHODS: Cardiac patches were generated from poly(ester carbonate urethane) urea and porcine decellularized cardiac extracellular matrix. ADSCs constitutively expressing green fluorescent protein were established from F344 rats and transplanted as a cell sheet over the left ventricle 3 days after left anterior descending artery ligation with or without an overlying cardiac patch. Cardiac function was serially evaluated using echocardiography for 8 weeks, comparing groups with combined cells and patch (group C, n = 9), ADSCs alone (group A, n = 7), patch alone (group P, n = 6) or sham groups (n = 7). RESULTS: Much greater numbers of ADSCs survived in the C versus A groups (P < .01). At 8 weeks posttransplant, the percentage fibrotic area was lower (P < .01) in groups C and P compared with the other groups and vasculature in the peri-infarct zone was greater in group C versus other groups (P < .01), and hepatocyte growth factor expression was higher in group C than in other groups (P < .05). Left ventricular ejection fraction was higher in group C versus other groups. CONCLUSIONS: A biodegradable cardiac patch enhanced ADSC engraftment, which was associated with greater cardiac function and neovascularization in the peri-infarct zone following subacute myocardial infarction. Published by Elsevier Inc.