BioIntel Research Laboratory, Department of Chemical and Petroleum Engineering, School of Engineering, University of Kansas, Lawrence, KS 66045, USA.
Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45219, USA.
Acta Biomater. 2018 Mar 15;69:95-106. doi: 10.1016/j.actbio.2017.12.025. Epub 2017 Dec 24.
The objective of this study was to develop an injectable and biocompatible hydrogel that can deliver a cocktail of therapeutic biomolecules (secretome) secreted by human adipose-derived stem cells (hASCs) to the peri-infarct myocardium. Gelatin and Laponite® were combined to formulate a shear-thinning, nanocomposite hydrogel (nSi Gel) as an injectable carrier of secretome (nSi Gel+). The growth factor composition and the pro-angiogenic activity of the secretome were tested in vitro by evaluating the proliferation, migration and tube formation of human umbilical endothelial cells. The therapeutic efficacy of the nSi Gel + system was then investigated in vivo in rats by intramyocardial injection into the peri-infarct region. Subsequently, the inflammatory response, angiogenesis, scar formation, and heart function were assessed. Biocompatibility of the developed nSi Gel was confirmed by quantitative PCR and immunohistochemical tests which showed no significant differences in the level of inflammatory genes, microRNAs, and cell marker expression compared to the untreated control group. In addition, the only group that showed a significant increase in capillary density, reduction in scar area and improved cardiac function was treated with the nSi Gel+. Our in vitro and in vivo findings demonstrate the potential of this new secretome-loaded hydrogel as an alternative strategy to treat myocardial infarction.
Stem cell based-therapies represent a possible solution to repair damaged myocardial tissue by promoting cardioprotection, angiogenesis, and reduced fibrosis. However, recent evidence indicates that most of the positive outcomes are likely due to the release of paracrine factors (cytokines, growth factors, and exosomes) from the cells and not because of the local engraftment of stem cells. This cocktail of essential growth factors and paracrine signals is known as secretome can be isolated in vitro, and the biomolecule composition can be controlled by varying stem-cell culture conditions. Here, we propose a straightforward strategy to deliver secretome produced from hASCs by using a nanocomposite injectable hydrogel made of gelatin and Laponite®. The designed secretome-loaded hydrogel represents a promising alternative to traditional stem cell therapy for the treatment of acute myocardial infarction.
本研究旨在开发一种可注射的、生物相容的水凝胶，以将人脂肪来源干细胞（hASC）分泌的治疗性生物分子（分泌组）递送至梗死周边心肌。将明胶和 Laponite®结合在一起，制成一种剪切变稀的纳米复合水凝胶（nSi Gel），作为分泌组的可注射载体（nSi Gel+）。通过评估人脐静脉内皮细胞的增殖、迁移和管形成，在体外测试分泌组的生长因子组成和促血管生成活性。然后通过向梗死周边心肌内注射，在大鼠体内研究 nSi Gel+系统的治疗效果。随后，评估炎症反应、血管生成、瘢痕形成和心功能。通过定量 PCR 和免疫组织化学测试证实了所开发的 nSi Gel 的生物相容性，与未处理的对照组相比，其炎症基因、microRNA 和细胞标志物表达水平没有显著差异。此外，只有 nSi Gel+治疗组的毛细血管密度显著增加、瘢痕面积减少和心功能改善。我们的体外和体内研究结果表明，这种新型分泌组负载水凝胶具有作为治疗心肌梗死的替代策略的潜力。
