| Background Minimal change nephrosis (MCN)is a kind of podocyte cytopathy, which is a common pathological pattern of primary glomerulopathy in our country. It is characterized pathologically by normal light microscopy, the absence of immune deposits on immunoflurescence microscopy, and diffuse foot process effacement on electron microscopy. There is a severe functional defect in glomerular permselectivity due to abnormal slit diaphragm. Slit diaphragm between foot processes is the most important golmerular size and charge selective barrier. Genes of Slit diaphragm proteins such as nephrin and podocin are down-regulated in minimal change disease, which lead to damage of filtration barrier and massive proteinuria. Stem cells is self-renewal and has directional differentiation capability, which is an ideal choice in regeneration of the structure and function of tissues and organs. Mesenchymal stem cells (MSC) are multipotent stem cells rooted in early mesoderm, and could differentiate into bone cells, muscle cells, hepatic cells, kidney inherent cells and others. Moreover, MSCs can be cultured and amplified in vitro. Studies have shown that coisogenic mesenchymal stem cells can repair podocytes in rats with MCN, and human MSCs also improve damage of renal function in mice with acute kidney injury. Recently, researches on MSCs have been applied in treatment of diseases, such as leukemia, diabetes mellitus, myocardial infarction, Parkinson’s disease, lupus nephritis, which may lead to extensive clinical prospect.Objectives We measured plasma albumin, cholesterin, serum creatinine, blood urea nitrogen,24hr urine protein, and mRNA expression of nephrin after the injection of human umbilical cord mesenchymal stem cells (hUCMSCs) into rats with MCN. We also investigated the safety of intravenous (iv) injection of hUCMSCs, and its effects on proteinuria and repair of podocyte, and potential mechanisms in rats with MCN. Furthermore, this study may provide new evidence to pathogenesis and a potentially new approach to treatment of chronic kidney disease, especially nephrotic syndrome.Methods Sixty rats were randomly divided into blank control group (n=20), model group(n=20) and hUCMSCs intervention group (n=20). Each group was then randomly divided into10rats on day10and28of experiments. Model group and hUCMSCs intervention group received the injection of adriamycin (5mg/kg) via caudal vein in sequence. On the same day, hUCMSCs intervention group received an iv injection of lml hUCMSCs suspensions(1×107cells), and model group received an iv injection of1ml physiological saline. Blood,24hr urine and kidney tissue were preserved on10th and28th day. We then measured24hr urine total protein, plasma albumin, cholesterin, creatinine, blood urea nitrogen, nephrin mRNA by RT-PCR analysis, and examined kidney tissue under light microscope and electron microscope.Results1.On day10, among control group,24h urine total protein was (5.23±0.89) mg, plasma albumin was (34.53±2.17) g/1, cholesterin was (2.21±0.41) mmo/1, nephrin mRNA expression as nephrin/GAPDH was (0.78±0.01); among model group,24h urine total protein was (31.39±1.87) mg, plasma albumin was (22.48±1.27) g/1, cholesterin was (6.25±0.28) mmol/1, nephrin mRNA expression as nephrin/GAPDH was (0.47±0.01), plasma creatinine and blood urea nitrogen were normal. This indicates that minimal model group was established successfully; Among hUCMSCs intervention group,24hr urine total proteinwas (18.83±2.16) mg, plasma albumin was (24.76±.65) g/1, cholesterin was (6.14±0.67) mmol/1, nephrin mRNA expression as nephrin/GAPDH was (0.63±0.00), plasma creatinine and blood urea nitrogen were normal.There was statistical significance between model group and intervention group (P<0.05).2.On day28, among control group,24h urine total protein was (96.25±1.95) mg, plasma albumin was(13.46+2.13)g/1,cholesterin was (8.57+0.42) mmol/1, nephrin mRNA expression as nephrin/GAPDH was (0.33+0.02), extensive podocyte foot process effacement was observed by electron microscope; among hUCMSCs intervention group,24h urine total proteinwas (33.76+1.54) mg; plasma albumin was; cholesterin was (5.34+0.16) mmol/l; nephrin mRNA expression as nephrin/GAPDH was (0.72+0.01). There was statistical significance between two groups (P<0.05). Plasma creatinine and blood urea nitrogen were normal. No abnormality was identified on light microscope, and extensive podocyte foot process effacement was observed on electron microscope in model group, compared with partial podocyet foot process effacement in hUCMSCs intervention group and no podocyet foot process effacement in blank control group.Conclusion In rats with MCN, hUCMSCs can repair damaged podocytes, reduce24hr proteinuria,decrease level of cholesterin, increase level of plasma albumin, up-regulate expression of nephrin mRNA. The potential mechanism may involve paracrine action, direct differentiation and microenvironmental improvement of renal peritubular capillaries by stem cells. |
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