Physiology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Centre of Excellence in Molecular and Cellular Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Physiol Rep. 2022 Sep;10(17):e15448. doi: 10.14814/phy2.15448.
Chronic kidney disease (CKD) is a priority health problem affecting 36% of Egyptians. Adipose-derived mesenchymal stem cells (ADMSCs) have multidifferentiation capacity and the ability to restore several types of cells including damaged renal cells. Granulocyte colony-stimulating factor (G-CSF) is known to mobilize hematopoietic stem cells from bone marrow to the peripheral circulation. The aim of this study was to compare the effect of endogenous CD34 cells mobilization and exogenous ADMSCs administration in the treatment of a rat model of adriamycin (ADR)-induced CKD. A total of 48 male albino rats of the local strain (200 ± 50 g) were equally divided into four groups: control negative, ADR (control positive), ADMSCs group, and G-CSF group. Six rats from each group were sacrificed after 4 weeks and the other 6 after 12 weeks. Renal function was assessed frequently by measuring serum creatinine, albumin, urea, 24-h urinary protein level, and hemoglobin level throughout the study. Oxidative stress markers malondialdehyde (MDA) and total antioxidant (TAO) were measured on day 28. CD-34 cell percentage was measured on day 9. After the sacrification of the rats, kidneys were removed for histopathological assessment. Results revealed that both ADMSCs and G-CSF significantly improved serum creatinine, albumin, urea, 24-h urinary protein level, and histopathological damage score, with the G-CSF-treated group showing better improvement in 24-h urinary protein level, serum albumin, and histopathological damage score compared with ADMSCs-treated group. The G-CSF group also had significantly higher levels of CD34 cells. Oxidative stress markers (MDA and TAO) levels were significantly improved with both therapies. We conclude that mobilization of endogenous hematopoietic stem cells by G-CSF is more effective than exogenously injected ADMSCs in protecting the kidneys against AD-induced toxicity.
慢性肾病（CKD）是影响 36%埃及人的优先健康问题。脂肪间充质干细胞（ADMSCs）具有多向分化能力和修复多种类型细胞的能力，包括受损的肾细胞。粒细胞集落刺激因子（G-CSF）已知能将造血干细胞从骨髓动员到外周循环。本研究旨在比较内源性 CD34 细胞动员和外源性 ADMSCs 给药在阿霉素（ADR）诱导的 CKD 大鼠模型治疗中的作用。总共 48 只雄性白化大鼠（本地品系，200±50g）平均分为四组：阴性对照组、ADR（阳性对照组）、ADMSCs 组和 G-CSF 组。每组 6 只大鼠在 4 周后和其余 6 只大鼠在 12 周后被处死。在整个研究过程中，通过频繁测量血清肌酐、白蛋白、尿素、24 小时尿蛋白水平和血红蛋白水平来评估肾功能。在第 28 天测量氧化应激标志物丙二醛（MDA）和总抗氧化（TAO）。在第 9 天测量 CD-34 细胞百分比。大鼠死后取出肾脏进行组织病理学评估。结果表明，ADMSCs 和 G-CSF 均显著改善了血清肌酐、白蛋白、尿素、24 小时尿蛋白水平和组织病理学损伤评分，与 ADMSCs 治疗组相比，G-CSF 治疗组 24 小时尿蛋白水平、血清白蛋白和组织病理学损伤评分改善更明显。G-CSF 组的 CD34 细胞水平也显著升高。两种治疗方法均显著改善了氧化应激标志物（MDA 和 TAO）水平。我们得出结论，G-CSF 动员内源性造血干细胞比外源性注射 ADMSCs 更有效地保护肾脏免受 AD 诱导的毒性。
