Biochemical and histopathological evaluations of chronic renal failure rats treated with pluripotent human stem cells

Abstract Regeneration of damaged kidney cells using stem cells is the current research approach in the treatment of chronic renal failure (CRF). In the present study, the histopathological and biochemical techniques were used to evaluate stem cells’ (SCs) role in treatment of CRF. Sixty-four rats were divided into eight groups. Group I (GI): rats were injected with doxorubicin (15 mg/kg) to initiate CRF. GII-GVII: rats were injected with doxorubicin and treated with SCs (1x106 MSCs or/and 2x104 HSCs/rat) with/without growth factors extract (200 µL/rat) and/or immunosuppressor (cyclosporine A, 5 mg/kg/day). GVIII: rats treated with PBS (100 µL/kg/day). Levels of creatinine, urea and uric acid were increased in rats sera after injection with doxorubicin, while blood electrolyte levels of Na, K, P and Mg were decreased. Also, histopathological abnormalities such as hyalinized blood vessels, degenerated hyalinized glomerulus tubules and cell debris in the lumen and degeneration of renal tissues were observed in these rats. After treatment with SCs, all these parameters restore their normal values with regeneration of the damaged cells as demonstrated in histopathology of the treated groups. It can be concluded that, the use of SCs in treatment of kidney diseases is a promising approach and needs more efforts.

摘要：利用干细胞再生受损肾细胞是当前慢性肾衰竭（chronic renal failure, CRF）治疗领域的研究方向之一。本研究采用组织病理学与生化检测技术，评估干细胞（stem cells, SCs）在慢性肾衰竭治疗中的作用。将64只大鼠随机分为8组：第1组（GI）：向大鼠注射阿霉素（15 mg/kg）以构建慢性肾衰竭模型。第2至7组（GII~GVII）：大鼠先注射阿霉素造模，随后分别给予干细胞制剂[1×10⁶个间充质干细胞（mesenchymal stem cells, MSCs）或/和2×10⁴个造血干细胞（hematopoietic stem cells, HSCs）/只]，联合或不联合生长因子提取物（200 μL/只）及/或免疫抑制剂环孢素A（cyclosporine A，5 mg/kg/天）。第8组（GVIII）：给予磷酸盐缓冲液（Phosphate Buffered Saline, PBS，100 μL/kg/天）作为空白对照。阿霉素注射造模后，大鼠血清中肌酐、尿素及尿酸水平显著升高，而血清钠（Na）、钾（K）、磷（P）及镁（Mg）等电解质水平则显著降低；同时，该组大鼠的肾组织病理学检测可见多种异常改变：血管透明样变、肾小球与肾小管透明样变性、管腔内出现细胞碎屑沉积，以及肾组织退行性变。经干细胞治疗后，上述各项检测指标均恢复至正常水平，受损肾细胞得以再生，治疗组的肾组织病理学结果证实了这一结论。综上，干细胞用于肾脏疾病治疗是一种极具前景的治疗方案，仍有待开展更多深入研究。