Institute for Advanced Chemistry of Catalonia, Barcelona 08034, Spain; Networking Biomedical Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
Int J Cardiol. 2013 Nov 15;169(4):288-95. doi: 10.1016/j.ijcard.2013.09.013. Epub 2013 Oct 6.
Adipose tissue-derived progenitor cells (ATDPCs) isolated from human cardiac adipose tissue are useful for cardiac regeneration in rodent models. These cells do not express cardiac troponin I (cTnI) and only express low levels of PECAM-1 when cultured under standard conditions. The purpose of the present study was to evaluate changes in cTnI and PECAM-1 gene expression in cardiac ATDPCs following their delivery through a fibrin patch to a murine model of myocardial infarction using a non-invasive bioluminescence imaging procedure.
Cardiac and subcutaneous ATDPCs were doubly transduced with lentiviral vectors for the expression of chimerical bioluminescent-fluorescent reporters driven by constitutively active and tissue-specific promoters (cardiac and endothelial for cTnI and PECAM-1, respectively). Labeled cells mixed with fibrin were applied as a 3-D fibrin patch over the infarcted tissue. Both cell types exhibited de novo expression of cTnI, though the levels were remarkably higher in cardiac ATDPCs. Endothelial differentiation was similar in both ATDPCs, though cardiac cells induced vascularization more effectively. The imaging results were corroborated by standard techniques, validating the use of bioluminescence imaging for in vivo analysis of tissue repair strategies. Accordingly, ATDPC treatment translated into detectable functional and morphological improvements in heart function.
Both ATDPCs differentiate to the endothelial lineage at a similar level, cardiac ATDPCs differentiated more readily to the cardiomyogenic lineage than subcutaneous ATDPCs. Non-invasive bioluminescence imaging was a useful tool for real time monitoring of gene expression changes in implanted ATDPCs that could facilitate the development of procedures for tissue repair.
从人心房脂肪组织中分离得到的脂肪组织源性祖细胞（ATDPC）在啮齿动物模型中对心脏再生有用。这些细胞在标准条件下培养时不表达心肌肌钙蛋白 I（cTnI），仅低水平表达 PECAM-1。本研究的目的是使用非侵入性生物发光成像程序，通过纤维蛋白贴剂将心脏 ATDPC 递送至心肌梗死的鼠模型中，评估其在心肌梗死后 cTnI 和 PECAM-1 基因表达的变化。
心脏和皮下 ATDPC 均被慢病毒载体双重转导，以表达由组成型激活和组织特异性启动子（心脏和内皮用于 cTnI 和 PECAM-1）驱动的嵌合生物发光-荧光报告基因。标记的细胞与纤维蛋白混合，作为 3-D 纤维蛋白贴剂应用于梗死组织。两种细胞类型均表现出 cTnI 的从头表达，尽管心脏 ATDPC 中的水平明显更高。两种 ATDPC 均表现出类似的内皮分化，但心脏细胞更有效地诱导血管生成。成像结果通过标准技术得到证实，验证了生物发光成像在体内组织修复策略分析中的应用。因此，ATDPC 治疗可导致心脏功能的可检测的功能和形态改善。
两种 ATDPC 均以相似的水平分化为内皮谱系，心脏 ATDPC 比皮下 ATDPC 更容易分化为心肌生成谱系。非侵入性生物发光成像技术是实时监测植入 ATDPC 中基因表达变化的有用工具，有助于开发组织修复程序。
