Department of Pediatric, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
Int J Mol Sci. 2021 Dec 29;23(1):344. doi: 10.3390/ijms23010344.
Glomerular endothelial injury and effectiveness of glomerular endothelial repair play a crucial role in the progression of glomerulonephritis. Although the potent immune suppressive everolimus is increasingly used in renal transplant patients, adverse effects of its chronic use have been reported clinically in human glomerulonephritis and experimental renal disease. Recent studies suggest that progenitor stem cells could enhance glomerular endothelial repair with minimal adverse effects. Increasing evidence supports the notion that stem cell therapy and regenerative medicine can be effectively used in pathological conditions within the predictive, preventive and personalized medicine (PPPM) paradigm. In this study, using an experimental model of glomerulonephritis, we tested whether bone marrow-derived stem cells (BMDSCs) could provide better effect over everolimus in attenuating glomerular injury and improving the repair process in a rat model of glomerulonephritis. Anti-Thy1 glomerulonephritis was induced in male Sprague Dawley rats by injection of an antibody against Thy1, which is mainly expressed on glomerular mesangial cells. Additional groups of rats were treated with the immunosuppressant everolimus daily after the injection of anti-Thy1 or injected with single bolus dose of BMDSCs after one week of injection of anti-Thy1 (n = 6-8). Nine days after injection of anti-Thy1, glomerular albumin permeability and albuminuria were significantly increased when compared to control group ( < 0.05). Compared to BMDSCs, everolimus was significantly effective in attenuating glomerular injury, nephrinuria and podocalyxin excretion levels as well as in reducing inflammatory responses and apoptosis. Our findings suggest that bolus injection of BMDSCs fails to improve glomerular injury whereas everolimus slows the progression of glomerular injury in Anti-Thy-1 induced glomerulonephritis. Thus, everolimus could be used at the early stage of glomerulonephritis, suggesting potential implications of PPPM in the treatment of progressive renal injury.
肾小球内皮损伤和肾小球内皮修复的效果在肾小球肾炎的进展中起着至关重要的作用。尽管强效免疫抑制剂依维莫司在肾移植患者中越来越多地被使用，但在人类肾小球肾炎和实验性肾病中，已有临床报道其长期使用的不良反应。最近的研究表明，祖细胞干细胞可以增强肾小球内皮修复，且不良反应最小。越来越多的证据支持这样一种观点，即干细胞治疗和再生医学可以在预测、预防和个性化医学（PPPM）范式内的病理条件下有效地使用。在这项研究中，我们使用肾小球肾炎的实验模型，测试了骨髓来源的干细胞（BMDSCs）是否可以在减轻肾小球损伤和改善肾小球肾炎大鼠模型的修复过程方面提供比依维莫司更好的效果。雄性 Sprague Dawley 大鼠通过注射针对 Thy1 的抗体诱导抗 Thy1 肾小球肾炎，Thy1 主要在肾小球系膜细胞上表达。在注射抗 Thy1 后，另外几组大鼠每天接受免疫抑制剂依维莫司治疗，或在注射抗 Thy1 后一周内单次注射 BMDSCs（n = 6-8）。在注射抗 Thy1 后 9 天，与对照组相比，肾小球白蛋白通透性和白蛋白尿显著增加（<0.05）。与 BMDSCs 相比，依维莫司在减轻肾小球损伤、nephrinuria 和 podocalyxin 排泄水平以及减少炎症反应和细胞凋亡方面更有效。我们的研究结果表明，BMDSCs 的单次注射不能改善肾小球损伤，而依维莫司可减缓抗 Thy1 诱导的肾小球肾炎中肾小球损伤的进展。因此，依维莫司可用于肾小球肾炎的早期阶段，提示 PPPM 在治疗进行性肾损伤方面具有潜在意义。
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