| Objective: To compare the biological characteristics between urine-derived stem cells(USC)from patients with chronic kidney disease and USC of healthy people,to explore whether USC can be used as a biomarker to evaluate renal regeneration potential in chronic kidney disease,and to explore the feasibility of using USC as autologous seed cells in the treatment of chronic kidney disease,and to observe the protective effect of USC on renal function of early chronic kidney disease.Methods: Diabetic nephropathy as the representative disease of chronic kidney disease,USC were isolated from urine samples of 12 male diabetic nephropathy patients and 10 healthy men of the same age.USC from patients with diabetic nephropathy(d-USC)and healthy men were cultured and identified,in addition to comparing regenerative capacity including proliferation,paracrine and differentiation ability of two groups of USC,we studied biological factors that might explain these differences in regenerative function,with an emphasis on the m-TOR signaling pathway,autophagy level,cellular inflammatory,redox properties and cell apoptosis.Streptozotocin(STZ)-induced NOD/SCID mouse model of early-staged diabetic nephropathy received an intraperitoneal injection of USC from healthy men for three times on 10 th,17th and 24 th days after the beginning of model establishment,the changes of body weight and blood sugar of the mice were monitored.On the 32 nd day,renal function of the mice was detected and samples were collected for histological examination to observe the pathological changes of the kidney.Results: 1.A large amount of USC(d-USC)can still be cultured in the urine of diabetic nephropathy patients,and d-USC was the same as that of healthy men to express mesenchymal stem cell markers including CD 44,CD 73,CD 90 and CD 105,but not the hematopoietic stem cell markers such as CD31,CD34 and CD45,the karyotype is normal,but up to nearly 70% of the d-USC have impaired quality;2.The regenerative capacity of d-USC,including proliferation capacity,production of nutrient factors and renal tubule epithelial differentiation capacity,was significantly reduced;3.The telomerase activity of d-USC decreased significantly and m-TOR signaling pathway was inhibited,d-USC had reduced autophagy level and increased levels of inflammatory factors,apoptosis and oxidative stress markers;4.Transplantation of USC through intraperitoneal injection in mouse model of early-staged diabetic nephropathy can reduce blood glucose,improve renal function and tissue structure,alleviate inflammation and oxidative stress,reduce renal interstitial fibrosis.Conclusion: 1.The regenerative capacity of USC from patients with chronic kidney disease(such as diabetic nephropathy),including proliferation,paracrine and differentiation capacity,was significantly reduced due to the decreased telomerase activity and the alleviating inflammation,oxidative stress and apoptosis,reflecting a reduced capacity for kidney injury repair in patients with chronic kidney disease;2.The patient-derived USC could be used for modeling the cell biology of diabetic nephropathy and as a tool to predict poor outcome in patients with diabetic nephropathy and other chronic kidney disease.3.Intraperitoneal transplantation of urine-derived stem cells can effectively reduce renal impairment in early chronic kidney disease and promote the repair of injured kidney tissue. |
PDF Full Text Request