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.
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.
J Thorac Cardiovasc Surg. 2022 Apr;163(4):e261-e272. doi: 10.1016/j.jtcvs.2020.04.150. Epub 2020 May 18.
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.
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).
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.
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.
脂肪来源的干细胞（ADSCs）在心脏再生中显示出良好的前景，但稳定的植入仍然具有挑战性。去细胞生物工程心脏补片在积极改变缺血性心肌病的心室重构方面显示出良好的前景。我们假设，与单独使用任何一种治疗方法相比，将 ADSC 片方法与生物工程补片相结合，在大鼠缺血性心肌病模型中，可增强 ADSC 植入并积极促进心脏功能。
心脏补片由聚（碳酸酯碳酸酯）尿烷和猪去细胞化心脏细胞外基质制成。从 F344 大鼠中建立了持续表达绿色荧光蛋白的 ADSC，并在左前降支结扎后 3 天，将其作为细胞片移植到左心室上方，与覆盖的心脏补片一起或不与心脏补片一起。使用超声心动图连续 8 周评估心脏功能，比较联合细胞和补片组（C 组，n=9）、ADSC 单独组（A 组，n=7）、补片单独组（P 组，n=6）或假手术组（n=7）。
与 A 组相比，C 组中的 ADSC 存活数量更多（P<.01）。在移植后 8 周时，与其他组相比，C 组和 P 组的纤维化面积百分比较低（P<.01），梗死周边区的血管密度较大（P<.01），且 C 组的肝细胞生长因子表达高于其他组（P<.05）。与其他组相比，C 组的左心室射血分数更高。
可生物降解的心脏补片增强了 ADSC 的植入，这与亚急性心肌梗死后梗死周边区的心脏功能和新生血管化增强有关。
