Hormones Department, National Research Centre, Giza, Egypt.
Stem Cell Lab., Centre of Excellence for Advanced Science, National Research Centre, Dokki, Giza, Egypt.
Appl Biochem Biotechnol. 2019 Sep;189(1):284-304. doi: 10.1007/s12010-019-02995-2. Epub 2019 Apr 12.
Acute kidney injury (AKI) is a rapid loss of renal function. It has high mortality rates. Still, renal replacement therapy is considered the best solution for recovering AKI. This opens a line of thought to develop an alternative therapy for it without complications. Mesenchymal stem cells are considered a new therapy for treating kidney diseases. The aim of this work was to address the anti-apoptotic, antioxidative, and pro-angiogenic effects of adipose tissue-derived MSCs (AD-MSCs) and bone marrow-MSCs (BM-MSCs) for treating AKI. Adult male Wistar rats were assigned into nine groups (n = 10): (1) the control group; (2) the AKI group, receiving cisplatin; (3) the AKI group treated with AD-MSCs (1 × 10); (4) the AKI group treated with AD-MSCs (2 × 10); (5) the AKI group treated with AD-MSCs (4 × 10); (6) the AKI group treated with losartan; (7) the AKI group treated with BM-MSCs (1 × 10); (8) the AKI group treated with BM-MSCs (2 × 10); and (9) the AKI group treated with BM-MSCs (4 × 10). The results showed a significant rise in creatinine, urea, and cystatin C (cys C) levels and upregulation of p38 mRNA, whereas a significant decline in NAD(P)H quinone oxidoreductase 1 (NQO-1) protein and downregulation of B-cell lymphoma-2 (Bcl-2) mRNA and vascular endothelial growth factor (VEGF) mRNA were recorded in AKI. MSCs could improve renal functions manifested by decreased urea, creatinine, and cys C levels; downregulation of p38; and upregulation of Bcl-2 and VEGF. Moreover, MSC therapy could induce NQO-1 in the treated rats relative to the untreated rats. So, cell-based therapy can reduce AKI through the antioxidative, anti-apoptotic, and pro-angiogenic properties of MSCs. Therefore, the findings received in this attempt create a fertile base for the setup of cell therapy in patients with AKI.
急性肾损伤(AKI)是肾功能的快速丧失。它的死亡率很高。尽管如此,肾替代疗法被认为是恢复 AKI 的最佳解决方案。这为开发一种无并发症的替代疗法开辟了思路。间充质干细胞被认为是治疗肾脏疾病的一种新疗法。本工作旨在探讨脂肪组织来源的间充质干细胞(AD-MSCs)和骨髓间充质干细胞(BM-MSCs)对 AKI 的抗凋亡、抗氧化和促血管生成作用。成年雄性 Wistar 大鼠分为 9 组(n=10):(1)对照组;(2)接受顺铂的 AKI 组;(3)AD-MSCs(1×10)处理的 AKI 组;(4)AD-MSCs(2×10)处理的 AKI 组;(5)AD-MSCs(4×10)处理的 AKI 组;(6)洛沙坦处理的 AKI 组;(7)BM-MSCs(1×10)处理的 AKI 组;(8)BM-MSCs(2×10)处理的 AKI 组;(9)BM-MSCs(4×10)处理的 AKI 组。结果显示,肌酐、尿素和胱抑素 C(cys C)水平显著升高,p38mRNA 上调,而 NAD(P)H 醌氧化还原酶 1(NQO-1)蛋白显著下降,B 细胞淋巴瘤-2(Bcl-2)mRNA 和血管内皮生长因子(VEGF)mRNA 下调。MSCs 可改善肾功能,表现为尿素、肌酐和 cys C 水平降低,p38 下调,Bcl-2 和 VEGF 上调。此外,与未治疗组相比,MSC 治疗可诱导治疗大鼠 NQO-1。因此,基于细胞的治疗可通过 MSC 的抗氧化、抗凋亡和促血管生成特性来减轻 AKI。因此,本研究的结果为 AKI 患者的细胞治疗奠定了基础。