Autologous cell therapy for cisplatin-induced acute kidney injury by using non-expanded adipose tissue-derived cells
Autologous cell therapy for cisplatin-induced acute kidney injury by using non-expanded adipose tissue-derived cells
复制标题
DOI：
10.3109/14653249.2012.693157
复制
发表时间：
2012-10-01
期刊：
影响因子：
4.5
通讯作者：
Maruyama, Shoichi
中科院分区：
文献类型：
--
作者：
Yasuda, Kaoru;Ozaki, Takenori;Maruyama, Shoichi
背景目标。最近的研究表明，脂肪组织来源的培养的间充质基质细胞对再生细胞治疗是有用的。间质血管分数(SVF)无需培养即可获得，具有临床应用价值。我们观察了SVF的疗效，并将其应用于急性肾损伤(AKI)的治疗。方法：研究方法。抽脂吸入物来自提供书面知情同意的健康捐赠者。收集SVF，用条件培养液测定其生长因子分泌和抗凋亡能力。为探讨SVF对AKI的影响，将SVF注射到大鼠肾皮质下，观察SVF对AKI的影响。结果。人和大鼠SVF细胞均可分泌血管内皮生长因子-A(VEGF)和肝细胞生长因子(HGF)。人SVF条件培养液具有抗细胞凋亡作用，该作用可被抗HGF抗体抑制，但不能被抗血管内皮生长因子抗体抑制。在体内，SVF可明显改善肾功能，减轻肾小管损伤，增加皮质血流速度。在SVF治疗组中，皮质中的血管内皮生长因子水平以及皮质和髓质中的HGF水平均显著高于对照组，尤其是髓质中的小管。免疫组织化学染色显示SVF细胞表达血管内皮生长因子和肝细胞生长因子，第14天仍留在囊膜下。目前的研究表明，未扩张的SVF细胞被膜下注射可改善大鼠AKI，其机制可能与肾保护分子的分泌有关。人SVF作为一种治疗肾脏疾病的新型自体细胞疗法，有可能在临床上得到应用。
Background aims. Recent studies have demonstrated that cultured mesenchymal stromal cells derived from adipose tissue are useful for regenerative cell therapy. The stromal vascular fraction (SVF) can be obtained readily without culturing and may be clinically applicable. We investigated the therapeutic effects of SVF and used it in the treatment of acute kidney injury (AKI). Methods. Liposuction aspirates were obtained from healthy donors who had provided written informed consent. We harvested the SVF and determined the growth factor secretion and anti-apoptotic ability with conditioned medium. To investigate the effect of SVF on AKI, cisplatin was injected into rats and SVF was administrated into the subcupsula of the kidney. Results. Both human and rat SVF cells secreted vascular endothelial growth factor-A (VEGF) and hepatocyte growth factor (HGF). Human SVF-conditioned media had an anti-apoptotic effect, which was inhibited by anti-HGF antibody (Ab) but not by anti-VEGF Ab. In vivo, SVF significantly ameliorated renal function, attenuated tubular damage and increased the cortical blood flow speed. In the SVF-treated group, VEGF levels in the cortex and HGF levels in both the cortex and medulla, especially tubules in the medulla, were significantly higher. Immunostaining revealed that SVF cells expressing VEGF and HGF and remained in the subcapsule on day 14. Conclusions. The present study demonstrates that a subcapsular injection of non-expanded SVF cells ameliorates rat AKI, and that the mechanism probably involves secretion of renoprotective molecules. Administration of human SVF may be clinically applicable and useful as a novel autologous cell therapy against kidney diseases.