Heart Failure and Cardiac Regeneration (ICREC) Research Program, Health Research Institute Germans Trias i Pujol (IGTP), Cardiology Service, Hospital Universitari Germans Trias i Pujol Badalona, Spain.
Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill Genetic Medicine Building, Chapel Hill NC, USA.
Am J Transl Res. 2014 May 15;6(3):291-301. eCollection 2014.
Contractile restoration of myocardial scars remains a challenge with important clinical implications. Here, a combination of porous elastomeric membrane, peptide hydrogel, and subcutaneous adipose tissue-derived progenitor cells (subATDPCs) was designed and evaluated as a bioimplant for cardiac regeneration in a mouse model of myocardial infarction. SubATDPCs were doubly transduced with lentiviral vectors to express bioluminescent-fluorescent reporters driven by constitutively active, cardiac tissue-specific promoters. Cells were seeded into an engineered bioimplant consisting of a scaffold (polycaprolactone methacryloyloxyethyl ester) filled with a peptide hydrogel (PuraMatrix™), and transplanted to cover injured myocardium. Bioluminescence and fluorescence quantifications showed de novo and progressive increases in promoter expression in bioactive implant-treated animals. The bioactive implant was well adapted to the heart, and fully functional vessels traversed the myocardium-bioactive implant interface. Treatment translated into a detectable positive effect on cardiac function, as revealed by echocardiography. Thus, this novel implant is a promising construct for supporting myocardial regeneration.
心肌瘢痕的收缩性恢复仍然是一个具有重要临床意义的挑战。在这里,我们设计并评估了一种多孔弹性膜、肽水凝胶和皮下脂肪组织来源的祖细胞(subATDPC)的组合,作为心肌梗死后小鼠模型心脏再生的生物植入物。subATDPC 被双转导慢病毒载体,以表达由组成型激活、心脏组织特异性启动子驱动的生物发光-荧光报告基因。将细胞接种到由支架(聚己内酯甲基丙烯酸酯)填充肽水凝胶(PuraMatrix™)组成的工程生物植入物中,并移植到损伤的心肌上。生物发光和荧光定量显示,在生物活性植入物治疗的动物中,启动子表达呈新出现和渐进性增加。生物活性植入物与心脏很好地适应,并且完全功能性的血管穿过心肌-生物活性植入物界面。超声心动图显示,这种治疗方法对心脏功能产生了可检测的积极影响。因此,这种新型植入物是一种很有前途的支持心肌再生的构建体。