Modulatory and regenerative potential of transplanted bone marrow-derived mesenchymal stem cells on rifampicin-induced kidney toxicity

Modulatory and regenerative potential of transplanted bone marrow-derived mesenchymal stem cells on rifampicin-induced kidney toxicity
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DOI:
10.1016/j.reth.2018.09.001
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发表时间:
2018-12-01
影响因子:
4.3
通讯作者:
Subbiah, Suresh Kumar
Subbiah, Suresh Kumar
中科院分区:
工程技术3区
文献类型:
--
作者:
Danjuma, Lawal;Mok, Pooi Ling;Subbiah, Suresh Kumar

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前言:抗结核药物利福平因其有效性而被广泛使用。结核病和长期利福平治疗的可能并发症包括肾脏损害;这些情况可能导致受影响肾脏的效率降低,从而导致其他疾病。骨髓间充质干细胞(BMMSCs)可以与利福平联合使用以避免肾脏损伤,因为它具有再生和分化为肾脏细胞的潜力。本研究旨在评价骨髓间充质干细胞在避免利福平肾毒性对Wistar大鼠及其子代的肾损伤中的调节和再生潜能。方法:将大鼠分为3组:对照组(4只雄性,4只雌性),单纯利福平组(4只雄性,4只雌性),利福平+MSCs组(4只雄性,4只雌性),3组:利福平+MSCs组(4只雄性,4只雌性)。治疗剂量利福平(9 mg/kg/d,3个月)和骨髓间充质干细胞输注(2次/月,3个月)。在三个月结束时,这些动物被一起饲养,以确定这些影响是否会传递给下一代。结果:单纯利福平治疗组大鼠的生化指标和组织病理损伤程度均有不同程度的改变,而对照组和干细胞组的生化指标和正常组织结构均明显正常或接近正常水平。结论:从生化指标、组织学和细胞定量分析来看,静脉注射MSCs可获得合理的发育,表明MSCs具有调节和再生的特性。(C)2018年,日本再生医学学会。爱思唯尔B.V.制作和主办。
Introduction: Anti-tuberculosis agent rifampicin is extensively used for its effectiveness. Possible complications of tuberculosis and prolonged rifampicin treatment include kidney damage; these conditions can lead to reduced efficiency of the affected kidney and consequently to other diseases. Bone marrow-derived mesenchymal stem cells (BMMSCs) can be used in conjunction with rifampicin to avert kidney damage; because of its regenerative and differentiating potentials into kidney cells. This research was designed to assess the modulatory and regenerative potentials of MSCs in averting kidney damage due to rifampicin-induced kidney toxicity in Wistar rats and their progenies. BMMSCs used in this research were characterized according to the guidelines of International Society for Cellular Therapy.Methods: The rats (male and female) were divided into three experimental groups, as follows: Group 1: control rats (4 males & 4 females); Group 2: rats treated with rifampicin only (4 males & 4 females); and Group 3: rats treated with rifampicin plus MSCs (4 males & 4 females). Therapeutic doses of rifampicin (9 mg/kg/day for 3-months) and MSCs infusions (twice/month for 3-months) were administered orally and intravenously respectively. At the end of the three months, the animals were bred together to determine if the effects would carry over to the next generation. Following breeding, the rats were sacrificed to harvest serum for biochemical analysis and the kidneys were also harvested for histological analysis and quantification of the glomeruli size, for the adult rats and their progenies.Results: The results showed some level of alterations in the biochemical indicators and histopathological damage in the rats that received rifampicin treatment alone, while the control and stem cells treated group showed apparently normal to nearly normal levels of both bio-indicators and normal histological architecture.Conclusions: Intravenous administration of MSCs yielded sensible development, as seen from biochemical indicators, histology and the quantitative cell analysis, hence implying the modulatory and regenerative properties of MSCs. (C) 2018, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.