Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences , No. 27, Taiping Road, Beijing 100850, China.
Department of Polymer Science and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, China.
ACS Nano. 2017 Jun 27;11(6):5474-5488. doi: 10.1021/acsnano.7b00221. Epub 2017 Jun 12.
Stem cell implantation strategy has exhibited potential to treat the myocardial infarction (MI), however, the low retention and survival limit their applications due to the reactive oxygen species (ROS) microenvironment after MI. In this study, the fullerenol nanoparticles are introduced into alginate hydrogel to create an injectable cell delivery vehicle with antioxidant activity. Results suggest that the prepared hydrogels exhibit excellent injectable and mechanical strength. In addition, the fullerenol/alginate hydrogel can effectively scavenge the superoxide anion and hydroxyl radicals. Based on these results, the biological behaviors of brown adipose-derived stem cells (BADSCs) seeded in fullerenol/alginate hydrogel were investigated in the presence of HO. Results suggest that the fullerenol/alginate hydrogels have no cytotoxicity effects on BADSCs. Moreover, they can suppress the oxidative stress damage of BADSCs and improve their survival capacity under ROS microenvironment via activating the ERK and p38 pathways while inhibiting JNK pathway. Further, the addition of fullerenol can improve the cardiomyogenic differentiation of BADSCs even under ROS microenvironment. To assess its therapeutic effects in vivo, the fullerenol/alginate hydrogel loaded with BADSCs were implanted in the MI area in rats. Results suggest that the fullerenol/alginate hydrogel can effectively decrease ROS level in MI zone, improve the retention and survival of implanted BADSCs, and induce angiogenesis, which in turn promote cardiac functional recovery. Therefore, the fullerenol/alginate hydrogel can act as injectable cell delivery vehicles for cardiac repair.
干细胞移植策略已被证明具有治疗心肌梗死（MI）的潜力，但由于 MI 后活性氧（ROS）微环境的存在，其细胞保留率和存活率较低，限制了其应用。在本研究中，富勒醇纳米粒子被引入海藻酸钠水凝胶中，以创建具有抗氧化活性的可注射细胞输送载体。结果表明，所制备的水凝胶具有优异的可注射性和机械强度。此外，富勒醇/海藻酸钠水凝胶可以有效清除超氧阴离子和羟基自由基。基于这些结果，研究了在 HO 存在下，在富勒醇/海藻酸钠水凝胶中接种棕色脂肪来源的干细胞（BADSCs）的生物学行为。结果表明，富勒醇/海藻酸钠水凝胶对 BADSCs 没有细胞毒性作用。此外，它们可以通过激活 ERK 和 p38 通路，同时抑制 JNK 通路，抑制 BADSCs 的氧化应激损伤，提高其在 ROS 微环境中的存活能力。此外，添加富勒醇可以改善 BADSCs 在 ROS 微环境下的心肌生成分化。为了评估其在体内的治疗效果，将负载 BADSCs 的富勒醇/海藻酸钠水凝胶植入大鼠的 MI 区域。结果表明，富勒醇/海藻酸钠水凝胶可以有效降低 MI 区的 ROS 水平，提高植入的 BADSCs 的保留率和存活率，并诱导血管生成，从而促进心脏功能的恢复。因此，富勒醇/海藻酸钠水凝胶可以作为心脏修复的可注射细胞输送载体。
