Danjuma Lawal, Mok Pooi Ling, Higuchi Akon, Hamat Rukman Awang, Teh Seoh Wei, Koh Avin Ee-Hwan, Munusamy Murugan A, Arulselvan Palanisamy, Rajan Mariappan, Nambi Arivudai, Swamy K B, Vijayaraman Kiruthiga, Murugan Kadarkarai, Natarajaseenivasan Kalimuthusamy, Subbiah Suresh Kumar
Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
Department of Microbiology and Biotechnology, Faculty of Science, Federal University Duste, P.M.B 7156, Duste, Jigawa, Nigeria.
Regen Ther. 2018 Sep 25;9:100-110. doi: 10.1016/j.reth.2018.09.001. eCollection 2018 Dec.
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.
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.
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.
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.
抗结核药物利福平因其有效性而被广泛使用。结核病及利福平长期治疗可能的并发症包括肾脏损害;这些情况会导致受影响肾脏的功能降低,进而引发其他疾病。骨髓间充质干细胞(BMMSCs)可与利福平联合使用以避免肾脏损害;因其具有向肾细胞再生和分化的潜能。本研究旨在评估间充质干细胞在避免Wistar大鼠及其子代因利福平诱导的肾毒性而导致肾脏损害方面的调节和再生潜能。本研究中使用的骨髓间充质干细胞按照国际细胞治疗协会的指南进行了鉴定。
将大鼠(雄性和雌性)分为三个实验组,如下:第1组:对照大鼠(4只雄性和4只雌性);第2组:仅用利福平治疗的大鼠(4只雄性和4只雌性);第3组:用利福平加间充质干细胞治疗的大鼠(4只雄性和4只雌性)。分别经口和静脉给予治疗剂量的利福平(9毫克/千克/天,持续3个月)和间充质干细胞输注(每月两次,持续3个月)。在三个月结束时,将动物一起饲养以确定这些影响是否会延续到下一代。繁殖后,处死大鼠以采集血清进行生化分析,同时也采集肾脏进行组织学分析以及对成年大鼠及其子代的肾小球大小进行量化。
结果显示,单独接受利福平治疗的大鼠的生化指标和组织病理学损伤有一定程度的改变,而对照组和干细胞治疗组的生物指标水平明显正常或接近正常,且组织学结构正常。
从生化指标、组织学和定量细胞分析来看,静脉注射间充质干细胞产生了明显的改善,这意味着间充质干细胞具有调节和再生特性。