Renal Cells from Spermatogonial Germline Stem Cells Protect against Kidney Injury
Renal Cells from Spermatogonial Germline Stem Cells Protect against Kidney Injury
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DOI：
10.1681/asn.2013040367
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发表时间：
2014-02-01
影响因子：
13.6
通讯作者：
Altruda, Fiorella
中科院分区：
文献类型：
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作者：
De Chiara, Letizia;Fagoonee, Sharmila;Altruda, Fiorella
精原干细胞位于曲细精管内的特定位置，并不断产生分化的子细胞以产生精子。虽然精原干细胞是单能的，但这些细胞能够在体外自发地转化为生殖细胞来源的多能干细胞（GPSC）。GPSC具有胚胎干细胞的许多特性，并且具有高度可塑性，但其在组织再生中的治疗潜力尚未得到充分开发。使用一种新的肾上皮分化方案，我们获得了GPSC衍生的管状样细胞（GTC），在体外功能，通过跨上皮电阻分析证明。在小鼠中，缺血性肾损伤后注射的GTC归巢到肾实质，GTC治疗的小鼠表现出减少肾脏氧化应激，肾小管细胞凋亡和皮质损伤，并上调肾小管抗氧化酶血红素加氧酶-1的表达。缺血性损伤后6周，GTC治疗小鼠的肾脏纤维化和炎性浸润比溶剂治疗小鼠的肾脏少。总之，我们表明，GPSC可以分化成功能活跃的肾小管样细胞，在体内治疗预防慢性缺血性损伤，介绍了GPSC在再生细胞治疗中的潜在效用。
Spermatogonial stem cells reside in specific niches within seminiferous tubules and continuously generate differentiating daughter cells for production of spermatozoa. Although spermatogonial stem cells are unipotent, these cells are able to spontaneously convert to germline cell-derived pluripotent stem cells (GPSCs) in vitro. GPSCs have many properties of embryonic stem cells and are highly plastic, but their therapeutic potential in tissue regeneration has not been fully explored. Using a novel renal epithelial differentiation protocol, we obtained GPSC-derived tubular-like cells (GTCs) that were functional in vitro, as demonstrated through transepithelial electrical resistance analysis. In mice, GTCs injected after ischemic renal injury homed to the renal parenchyma, and GTC-treated mice showed reduced renal oxidative stress, tubular apoptosis, and cortical damage and upregulated tubular expression of the antioxidant enzyme hemeoxygenase-1. Six weeks after ischemic injury, kidneys of GTC-treated mice had less fibrosis and inflammatory infiltrate than kidneys of vehicle-treated mice. In conclusion, we show that GPSCs can be differentiated into functionally active renal tubular-like cells that therapeutically prevent chronic ischemic damage in vivo, introducing the potential utility of GPSCs in regenerative cell therapy.