BACKGROUND There is no established treatment to impede the progression or restore kidney function in human chronic kidney disease(CKD).AIM To examine the efficacy of cultured human CD34+cells with enhanced proliferati...BACKGROUND There is no established treatment to impede the progression or restore kidney function in human chronic kidney disease(CKD).AIM To examine the efficacy of cultured human CD34+cells with enhanced proliferating potential in kidney injury in mice.METHODS Human umbilical cord blood(UCB)-derived CD34+cells were incubated for one week in vasculogenic conditioning medium.Vasculogenic culture significantly increased the number of CD34+cells and their ability to form endothelial progenitor cell colony-forming units.Adenineinduced tubulointerstitial injury of the kidney was induced in immunodeficient non-obese diabetic/severe combined immunodeficiency mice,and cultured human UCB-CD34+cells were administered at a dose of 1×106/mouse on days 7,14,and 21 after the start of adenine diet.RESULTS Repetitive administration of cultured UCB-CD34+cells significantly improved the time-course of kidney dysfunction in the cell therapy group compared with that in the control group.Both interstitial fibrosis and tubular damage were significantly reduced in the cell therapy group compared with those in the control group(P<0.01).Microvasculature integrity was significantly preserved(P<0.01)and macrophage infiltration into kidney tissue was dramatically decreased in the cell therapy group compared with those in the control group(P<0.001).CONCLUSION Early intervention using human cultured CD34+cells significantly improved the progression of tubulointerstitial kidney injury.Repetitive administration of cultured human UCB-CD34+cells significantly improved tubulointerstitial damage in adenine-induced kidney injury in mice via vasculoprotective and anti-inflammatory effects.展开更多
BACKGROUND To date,no specific treatment has been established to reverse progressive chronic kidney disease(CKD).AIM To evaluate the safety and efficacy of autologous CD34^(+)cell transplantation in CKD patients who e...BACKGROUND To date,no specific treatment has been established to reverse progressive chronic kidney disease(CKD).AIM To evaluate the safety and efficacy of autologous CD34^(+)cell transplantation in CKD patients who exhibited a progressive decline in renal function.METHODS The estimated glomerular filtration rate(eGFR)at the beginning of the study was 15.0-28.0 mL/minute/1.73 m^(2).After five days of treatment with the granulocyte colony-stimulating factor,mononuclear cells were harvested and CD34^(+)cells were magnetically collected.CD34^(+)cells were directly injected into the bilateral renal arteries twice(at 0 and 3 months),and their safety and efficacy were evaluated for 6 months.RESULTS Four patients were enrolled and completed the study.Three of four patients showed improvement in eGFR slope(eGFR slope>0 mL/minute/1.73 m^(2)),with the monthly slope of eGFR(delta eGFR)changing from-1.36±1.1(pretreatment)to^(+)0.22±0.71(at 6 months)mL/minute/1.73 m^(2)/month(P=0.135)after cell therapy.Additionally,intrarenal resistive index(P=0.004)and shear wave velocity(P=0.04)were significantly improved after cell therapy.One patient experienced transient fever after cell therapy,and experienced bone pain during granulocyte colony-stimulating factor administration.However,no severe adverse events were reported.CONCLUSION In conclusion,our findings suggest that repetitive peripheral blood-derived autologous CD34^(+)cell transplantation into the renal arteries is safe,feasible,and may be effective for patients with progressive CKD.However,a large-scale clinical trial is warranted to validate the efficacy of repetitive regenerative cell therapy using autologous CD34^(+)cells in patients with progressive CKD.展开更多
文摘BACKGROUND There is no established treatment to impede the progression or restore kidney function in human chronic kidney disease(CKD).AIM To examine the efficacy of cultured human CD34+cells with enhanced proliferating potential in kidney injury in mice.METHODS Human umbilical cord blood(UCB)-derived CD34+cells were incubated for one week in vasculogenic conditioning medium.Vasculogenic culture significantly increased the number of CD34+cells and their ability to form endothelial progenitor cell colony-forming units.Adenineinduced tubulointerstitial injury of the kidney was induced in immunodeficient non-obese diabetic/severe combined immunodeficiency mice,and cultured human UCB-CD34+cells were administered at a dose of 1×106/mouse on days 7,14,and 21 after the start of adenine diet.RESULTS Repetitive administration of cultured UCB-CD34+cells significantly improved the time-course of kidney dysfunction in the cell therapy group compared with that in the control group.Both interstitial fibrosis and tubular damage were significantly reduced in the cell therapy group compared with those in the control group(P<0.01).Microvasculature integrity was significantly preserved(P<0.01)and macrophage infiltration into kidney tissue was dramatically decreased in the cell therapy group compared with those in the control group(P<0.001).CONCLUSION Early intervention using human cultured CD34+cells significantly improved the progression of tubulointerstitial kidney injury.Repetitive administration of cultured human UCB-CD34+cells significantly improved tubulointerstitial damage in adenine-induced kidney injury in mice via vasculoprotective and anti-inflammatory effects.
文摘BACKGROUND To date,no specific treatment has been established to reverse progressive chronic kidney disease(CKD).AIM To evaluate the safety and efficacy of autologous CD34^(+)cell transplantation in CKD patients who exhibited a progressive decline in renal function.METHODS The estimated glomerular filtration rate(eGFR)at the beginning of the study was 15.0-28.0 mL/minute/1.73 m^(2).After five days of treatment with the granulocyte colony-stimulating factor,mononuclear cells were harvested and CD34^(+)cells were magnetically collected.CD34^(+)cells were directly injected into the bilateral renal arteries twice(at 0 and 3 months),and their safety and efficacy were evaluated for 6 months.RESULTS Four patients were enrolled and completed the study.Three of four patients showed improvement in eGFR slope(eGFR slope>0 mL/minute/1.73 m^(2)),with the monthly slope of eGFR(delta eGFR)changing from-1.36±1.1(pretreatment)to^(+)0.22±0.71(at 6 months)mL/minute/1.73 m^(2)/month(P=0.135)after cell therapy.Additionally,intrarenal resistive index(P=0.004)and shear wave velocity(P=0.04)were significantly improved after cell therapy.One patient experienced transient fever after cell therapy,and experienced bone pain during granulocyte colony-stimulating factor administration.However,no severe adverse events were reported.CONCLUSION In conclusion,our findings suggest that repetitive peripheral blood-derived autologous CD34^(+)cell transplantation into the renal arteries is safe,feasible,and may be effective for patients with progressive CKD.However,a large-scale clinical trial is warranted to validate the efficacy of repetitive regenerative cell therapy using autologous CD34^(+)cells in patients with progressive CKD.
