Anan Hoda H, Zidan Rania A, Shaheen Mohammad A, Abd-El Fattah Enas A
Histology and Cell Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Histology and Cell Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Cytotherapy. 2016 Aug;18(8):970-984. doi: 10.1016/j.jcyt.2016.05.004.
Renal disease is a major health problem. Recent studies have reported the efficacy of stem cell therapy in nephropathy animal models.
This study was designed to investigate the therapeutic effectiveness of bone marrow-derived mesenchymal stromal cells (MSCs) versus losartan in the treatment of renal alterations induced by adriamycin (ADR).
Thirty-five adult male albino rats were divided into four groups. Group I was the control group. Group II (adriamycin-treated group),which included ten rats that were injected with a single dose of adriamycin (15 mg/kg) intraperitoneally, was subdivided into subgroup IIa and IIb and they were sacrificed 1 week and 5 weeks after adriamycin injection, respectively. Group III was the adriamycin + losartan-treated group and 1 week after adriamycin injection five rats received 10 mg/kg of losartan orally and daily for 4 weeks. Group IV was the adriamycin + MSC-treated group); five rats were injected with adriamycin as group II then supplied with MSCs at a dose of 1 × 10(6) cells suspended in 0.5 mL of phosphate-buffered saline (PBS) per rat in the tail vein 1 week after adriamycin injection. Rats of this group were sacrificed 4 weeks after the stem cell injection. Blood urea nitrogen and serum creatinine were measured. Samples from renal cortex were processed for light and electron microscope examination. As regards light microscope, sections were stained with hematoxylin and eosin (H-E), periodic acid-Schiff (PAS), masson trichrome, proliferating cell nuclear antigen (PCNA) and Caspase-3 immunohistochemical stains. Morphometrical and statistical analyses were also conducted.
Examination of adriamycin-treated group revealed deterioration of renal functions and various degrees of renal structural alterations as vacuolated cytoplasm, dark nuclei and detached epithelial lining. Administration of losartan partially improved ADR-induced kidney dysfunction, whereas MSCs denoted a more ameliorative role evidenced by structural and functional recovery.
MSCs have a relevant therapeutic potential against ADR-induced renal damage. MSCs may accomplish this role by decreasing caspase-3 expression and increasing proliferating cell nuclear antigen staining which influence the regeneration of the kidney.
肾脏疾病是一个主要的健康问题。最近的研究报道了干细胞疗法在肾病动物模型中的疗效。
本研究旨在调查骨髓间充质基质细胞（MSCs）与氯沙坦相比在治疗阿霉素（ADR）诱导的肾脏改变中的治疗效果。
35只成年雄性白化大鼠被分为四组。第一组为对照组。第二组（阿霉素治疗组）包括10只大鼠，腹腔注射单剂量阿霉素（15mg/kg），分别在阿霉素注射后1周和5周处死，并分为亚组IIa和IIb。第三组为阿霉素+氯沙坦治疗组，在阿霉素注射1周后，5只大鼠口服10mg/kg氯沙坦，每日1次，共4周。第四组为阿霉素+间充质干细胞治疗组；5只大鼠如第二组一样注射阿霉素，然后在阿霉素注射1周后经尾静脉给予每只大鼠剂量为1×10(6)个细胞且悬浮于0.5mL磷酸盐缓冲盐水（PBS）中的间充质干细胞。该组大鼠在干细胞注射4周后处死。测量血尿素氮和血清肌酐。对肾皮质样本进行光镜和电镜检查。至于光镜检查，切片用苏木精和伊红（H-E）、过碘酸希夫（PAS）、马松三色染色、增殖细胞核抗原（PCNA）和半胱天冬酶-3免疫组化染色。还进行了形态计量学和统计学分析。
阿霉素治疗组检查显示肾功能恶化以及各种程度的肾脏结构改变，如细胞质空泡化、细胞核深色化和上皮衬里脱落。氯沙坦的给药部分改善了阿霉素诱导的肾功能障碍，而间充质干细胞表现出更明显的改善作用，这通过结构和功能的恢复得到证明。
间充质干细胞对阿霉素诱导的肾损伤具有相关的治疗潜力。间充质干细胞可能通过降低半胱天冬酶-3表达和增加增殖细胞核抗原染色来发挥这一作用，从而影响肾脏的再生。
