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

Abstract

IntroductionAnti-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.MethodsThe 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.ResultsThe 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.ConclusionsIntravenous 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.

Nephroprotective Effect of Mesenchymal Stem Cell-Based Therapy of Kidney Disease Induced by Toxicants

“…A total of 18 studies [ 11 – 15 , 17 – 19 , 21 , 22 , 24 , 26 – 29 , 32 – 34 , 36 , 37 ] were selected to assess the effect of MSCs on BUN, and the results indicate that the difference between the MSC treatment and control groups was observed for 2-3, 4-5, 6-8, and ≥28 days (2-3 days: WMD = −25.08, 95% CI: -37.49, -12.67, P < 0.0001; 4-5 days: WMD = −45.71, 95% CI: -59.36, -32.05, P < 0.00001; 6-8 days: WMD = −57.55, 95% CI: -99.19, -15.91, P = 0.007; ≥28 days: WMD = −23.39, 95% CI: -36.39, -10.40, P = 0.0004; Figure 4 and Table 2 ). However, no difference was observed between the MSC treatment and control groups for 13-15 days (WMD = −13.40, 95% CI: -32.34, 5.54, P = 0.17; Figure 4 and Table 2 ).…”

Mesenchymal stem cells in tuberculosis therapy

“…В экспериментальной работе L. Danjuma и соавт. на здоровых крысах сравнивались гистологические и биохимические показатели в 3 группах: крысы, получавшие в качестве нефротоксичного препарата только рифампицин; крысы, которым этот препарат назначался в комплексе с МСК, и контрольные животные [34]. Результаты показали отчетливые изменения биохимических показателей и признаки гистопатологического повреждения (некроз клубочков, вакуолизация клеток канальцев) у особей, получавших монотерапию рифампицином, в то время как в остальных группах таких отклонений не выявлено.…”

The Use of Mesenchymal Stem Cells in the Complex Treatment of Kidney Tuberculosis (Experimental Study)

“…Fibrotic processes, typical of a long course of specific inflammation and its chronicity, contribute partially to ureterohydronephrotic transformation of the kidney, along with the formation of granulomas and their calcification. They are inevitable, on the one hand, due to the late diagnosis of nephrotuberculosis as mentioned above and, on the other hand, due to the nephrotoxic effect of anti-tubercular drugs [ 5 ].…”