Mitigating Ischemic Injury of Stem Cell-Derived Insulin-Producing Cells after Transplant.
Mitigating Ischemic Injury of Stem Cell-Derived Insulin-Producing Cells after Transplant.
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DOI：
10.1016/j.stemcr.2017.07.012
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发表时间：
2017-09-12
影响因子：
5.9
通讯作者：
Tang Q
中科院分区：
文献类型：
--
作者：
Faleo G;Russ HA;Wisel S;Parent AV;Nguyen V;Nair GG;Freise JE;Villanueva KE;Szot GL;Hebrok M;Tang Q
人类干细胞衍生的胰岛素产生细胞（SCIPC）的大规模体外分化的出现使我们更接近于使用干细胞技术治疗糖尿病。然而，数十年的胰岛移植经验表明，移植后缺血诱导的胰岛细胞死亡严重限制了治疗的疗效。目前尚不清楚人SCIPC对缺血的敏感程度。在这项研究中，我们发现超过一半的SCIPC在移植后不久死亡。营养剥夺和缺氧协同作用，杀死SCIPC在体外。氨基酸补充剂可能通过提供细胞能量将SCIPC从营养剥夺中拯救出来。在5%的生理氧张力下产生SCIPC，赋予其耐缺氧性，而不影响其分化或功能。分化过程中的生理氧习服和移植过程中的氨基酸补充双管齐下的策略显著改善了移植后SCIPC的存活率。干细胞衍生的胰岛素产生细胞（SCIPC）对缺血性损伤敏感氨基酸补充防止营养缺乏诱导的SCIPC死亡在生理氧水平下产生SCIPC保护它们免受缺氧这两种策略联合保护SCIPC移植物在移植后的体内活力移植后由于缺血性损伤导致的细胞死亡是糖尿病的成功β细胞替代疗法的主要障碍。在这一期的《干细胞报告》中，法雷奥、罗斯等人。分析了缺氧和营养剥夺对人类干细胞衍生的胰岛素产生细胞的影响，并制定了有效的策略来促进移植后的存活。
The advent of large-scale in vitro differentiation of human stem cell-derived insulin-producing cells (SCIPC) has brought us closer to treating diabetes using stem cell technology. However, decades of experiences from islet transplantation show that ischemia-induced islet cell death after transplant severely limits the efficacy of the therapy. It is unclear to what extent human SCIPC are susceptible to ischemia. In this study, we show that more than half of SCIPC die shortly after transplantation. Nutrient deprivation and hypoxia acted synergistically to kill SCIPC in vitro. Amino acid supplementation rescued SCIPC from nutrient deprivation, likely by providing cellular energy. Generating SCIPC under physiological oxygen tension of 5% conferred hypoxia resistance without affecting their differentiation or function. A two-pronged strategy of physiological oxygen acclimatization during differentiation and amino acid supplementation during transplantation significantly improved SCIPC survival after transplant. Stem cell-derived insulin-producing cells (SCIPC) are susceptible to ischemic injury Amino acid supplementation prevents nutrient-deprivation-induced SCIPC death Generation of SCIPC at physiological oxygen levels protects them against hypoxia Both strategies combined preserve SCIPC graft viability in vivo upon transplant Cell death after transplant due to ischemic injury is a major obstacle to successful β cell replacement therapy for diabetes. In this issue of Stem Cell Reports, Faleo, Russ et al. analyzed the effects of hypoxia and nutrient deprivation on human stem cell-derived insulin-producing cells and developed effective strategies to promote their survival after transplant.
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影响因子：
4.4
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