Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Autoimmune Diseases Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
BMC Endocr Disord. 2024 Jan 5;24(1):6. doi: 10.1186/s12902-023-01535-8.
Diabetic nephropathy and hepatopathy are health problems described by specific renal and hepatic structure and function disturbances. The protective effects of the stem cell secretome have been shown in several kidney and liver diseases. The current study aims to evaluate the capability of conditioned media derived from human Wharton's jelly mesenchymal stem cells (hWJ-MSCs-CM) to alleviate diabetic complications.
Twenty Sprague Dawley rats were made diabetic through injection of STZ (60 mg/kg, i.p.). At week 8, diabetic rats were divided into two groups: treated [DM + hWJ-MSCs-CM (500 µl/rat for three weeks, i.p.)] and not treated (DM). At the 11th week, three groups (control, DM, and DM + hWJ-MSCs-CM) were kept in metabolic cages, and urine was collected for 24 h. The serum samples were maintained for measuring fasting blood glucose (FBG) and kidney and liver functional analysis. The left kidney and liver parts were kept at -80 °C to assess apelin and transforming growth factor-beta (TGF-β) expression. The right kidney, pancreas, and liver parts were used for histopathologic evaluation.
DM was detected by higher FBG, microalbuminuria, increased albumin/creatinine ratio, and pancreas, renal, and hepatic structural disturbances. Diabetic hepatopathy was determined by increasing liver enzymes and decreasing total bilirubin. The TGF-β gene expression was significantly upregulated in the diabetic kidney and liver tissues. Apelin gene expression was significantly downregulated in the diabetic liver tissue but did not change in kidney tissue. Administration of hWJ-MSCs-CM improved renal and hepatic functional and structural disturbances. Moreover, CM therapy significantly decreased TGF-β expression and enhanced apelin expression in the kidney and liver tissues.
Human WJ-MSCs-CM may have protective effects on diabetic renal and hepatic complications. These effects may happen through the regulation of TGF-β and apelin signaling pathways.
糖尿病肾病和肝病是由特定的肾脏和肝脏结构和功能紊乱引起的健康问题。干细胞分泌液在几种肾脏和肝脏疾病中显示出了保护作用。本研究旨在评估人脐带来源间充质干细胞（hWJ-MSCs）条件培养基（hWJ-MSCs-CM）减轻糖尿病并发症的能力。
通过注射 STZ（60mg/kg，ip）将 20 只 Sprague Dawley 大鼠制成糖尿病。在第 8 周，糖尿病大鼠分为两组：治疗组（DM+hWJ-MSCs-CM（500μl/只，腹腔注射，持续 3 周）和未治疗组（DM）。在第 11 周，三组（对照组、DM 组和 DM+hWJ-MSCs-CM 组）被置于代谢笼中，收集 24 小时尿液。保存血清样本以测量空腹血糖（FBG）和肾功能、肝功能分析。将左肾和肝组织保存于-80°C，以评估apelin 和转化生长因子-β（TGF-β）的表达。将右肾、胰腺和肝组织用于组织病理学评估。
DM 通过升高的 FBG、微量白蛋白尿、白蛋白/肌酐比值升高以及胰腺、肾脏和肝脏结构紊乱来检测。糖尿病性肝损伤通过肝酶升高和总胆红素降低来确定。糖尿病肾脏和肝脏组织中 TGF-β 基因表达显著上调。糖尿病肝组织中 apelin 基因表达显著下调，但在肾脏组织中没有变化。hWJ-MSCs-CM 的给药改善了肾脏和肝脏的功能和结构紊乱。此外，CM 治疗显著降低了 TGF-β表达，并增强了肾脏和肝脏组织中的 apelin 表达。
人 WJ-MSCs-CM 可能对糖尿病肾脏和肝脏并发症具有保护作用。这些作用可能通过调节 TGF-β和 apelin 信号通路发生。
