University of Ottawa Heart Institute, Division of Cardiology, Department of Medicine , University of Ottawa , Ottawa , Canada K1Y4W7.
Division of Cardiac Surgery, Department of Surgery, University of Ottawa Heart Institute , University of Ottawa , Ottawa , Canada K1Y4W7.
ACS Nano. 2018 May 22;12(5):4338-4350. doi: 10.1021/acsnano.7b08881. Epub 2018 Apr 20.
Although cocooning explant-derived cardiac stem cells (EDCs) in protective nanoporous gels (NPGs) prior to intramyocardial injection boosts long-term cell retention, the number of EDCs that finally engraft is trivial and unlikely to account for salutary effects on myocardial function and scar size. As such, we investigated the effect of varying the NPG content within capsules to alter the physical properties of cocoons without influencing cocoon dimensions. Increasing NPG concentration enhanced cell migration and viability while improving cell-mediated repair of injured myocardium. Given that the latter occurred with NPG content having no detectable effect on the long-term engraftment of transplanted cells, we found that changing the physical properties of cocoons prompted explant-derived cardiac stem cells to produce greater amounts of cytokines, nanovesicles, and microRNAs that boosted the generation of new blood vessels and new cardiomyocytes. Thus, by altering the physical properties of cocoons by varying NPG content, the paracrine signature of encapsulated cells can be enhanced to promote greater endogenous repair of injured myocardium.
虽然在心肌内注射前将茧状衍生的心脏干细胞 (EDCs) 包埋在保护性纳米多孔凝胶 (NPG) 中可以提高细胞的长期保留率，但最终植入的 EDC 数量微不足道，不太可能对心肌功能和疤痕大小产生有益影响。因此，我们研究了改变胶囊内 NPG 含量以改变茧的物理性质而不影响茧尺寸的效果。增加 NPG 浓度可以提高细胞迁移和活力，同时改善细胞介导的损伤心肌修复。鉴于后者发生时，NPG 含量对移植细胞的长期植入没有可检测到的影响，我们发现改变茧的物理性质促使衍生自外植体的心脏干细胞产生更多的细胞因子、纳米囊泡和 microRNAs，从而促进新血管和新心肌细胞的生成。因此，通过改变 NPG 含量来改变茧的物理性质，可以增强包裹细胞的旁分泌特征，从而促进损伤心肌的更大程度的内源性修复。
