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 Accurate preoperative staging of gastric cancer(GC),a common malignant tumor worldwide,is critical for appropriate treatment plans and prognosis.Dynamic three-phase enhanced computed tomography(CT)scanning ...BACKGROUND Accurate preoperative staging of gastric cancer(GC),a common malignant tumor worldwide,is critical for appropriate treatment plans and prognosis.Dynamic three-phase enhanced computed tomography(CT)scanning for preoperative staging of GC has limitations in evaluating tumor angiogenesis.CD34,a marker on vascular endothelial cell surfaces,is promising in evaluating tumor angiogenesis.We explored the value of their combination for preoperative staging of GC to improve the efficacy and prognosis of patients with GC.Medical records of 106 patients with GC treated at the First People's Hospital of Lianyungang between February 2021 and January 2023 were retrospectively studied.All patients underwent three-phase dynamic contrast-enhanced CT scanning before surgery,and CD34 was detected in gastroscopic biopsy specimens.Using surgical and pathological results as the gold standard,the diagnostic results of three-phase dynamic contrast-enhanced CT scanning at different T and N stages were analyzed,and the expression of CD34-marked microvessel density(MVD)at different T and N stages was determined.The specificity and sensitivity of three-phase dynamic contrast-enhanced CT and CD34 in T and N staging were calculated;those of the combined diagnosis of the two were evaluated in parallel.Independent factors affecting lymph node metastasis were analyzed using multiple logistic regression.RESULTS The accuracy of three-phase dynamic contrast-enhanced CT scanning in diagnosing stages T1,T2,T3 and T4 were 68.00%,75.00%,79.41%,and 73.68%,respectively,and for diagnosing stages N0,N1,N2,and N3 were 75.68%,74.07%,85.00%,and 77.27%,respectively.CD34-marked MVD expression increased with increasing T and N stages.Specificity and sensitivity of three-phase dynamic contrast-enhanced CT in T staging were 86.79%and 88.68%;for N staging,89.06%and 92.86%;for CD34 in T staging,64.15%and 88.68%;and for CD34 in N staging,84.38%and 78.57%,respectively.Specificity and sensitivity of joint diagnosis in T staging were 55.68%and 98.72%,and N staging were 75.15%and 98.47%,respectively,with the area under the curve for diagnosis improving accordingly.According to multivariate analysis,a longer tumor diameter,higher pathological T stage,lower differ-entiation degree,and higher expression of CD34-marked MVD were independent risk factors for lymph node metastasis in patients with GC.CONCLUSION With high accuracy in preoperatively determining the invasion depth and lymph node metastasis of GC,CD34 expression and three-phase dynamic contrast-enhanced CT can provide a reliable basis for surgical resection.展开更多
CD34+ cells from human umbilical cord blood were purified by Dynal beads M-450 CD34 immunoselection system and cultured in the presence of various cytokines alone or in combination, including stem cell factor (SCF), i...CD34+ cells from human umbilical cord blood were purified by Dynal beads M-450 CD34 immunoselection system and cultured in the presence of various cytokines alone or in combination, including stem cell factor (SCF), interleukin-6 (IL-6) and erythropoietin (EPO). The results revealed that: (D In methylcellulose culture, the plating efficiencies of purified cord blood CD34+ cells were much different when stimulated by various cytokines. IL-6 alone had the lowest colo-ny yield, while the combination of SCF, IL-6 and EPO had the highest yield. ② In the suspension culture, IL-6 alone or IL-6 + EPO had little expanding effect on cord blood CD34+ celis, the other cytokine combinations could expand cord blood CD34+ celis at different Ievels. Among them, the combination of SCF, IL-6 and EPO had the maximal expanding effect on cord blood CD34+ celis, the number of progenitor celis peaked at day 21, about 29-fold increase and nucleated celis increased approximately 3676-fold at day 28. The expanding effect of展开更多
AIM:To assess the utility of an autologous CD34 + and CD133 + stem cells infusion as a possible therapeutic modality in patients with end-stage liver diseases.METHODS:One hundred and forty patients with endstage liver...AIM:To assess the utility of an autologous CD34 + and CD133 + stem cells infusion as a possible therapeutic modality in patients with end-stage liver diseases.METHODS:One hundred and forty patients with endstage liver diseases were randomized into two groups.Group 1,comprising 90 patients,received granulocyte colony stimulating factor for five days followed by autologous CD34 + and CD133 + stem cell infusion in the portal vein.Group 2,comprising 50 patients,received regular liver treatment only and served as a control group.RESULTS:Near normalization of liver enzymes and improvement in synthetic function were observed in 54.5% of the group 1 patients;13.6% of the patients showed stable states in the infused group.None of the patients in the control group showed improvement.No adverse effects were noted.CONCLUSION:Our data showed that a CD34 + and CD133 + stem cells infusion can be used as supportive treatment for end-stage liver disease with satisfactory tolerability.展开更多
AIM: To study the effect of mobilized peripheral blood autologous CD34 positive(CD34+) cell infusion in patients with non-viral decompensated cirrhosis.METHODS: Cirrhotic patients of non-viral etiology were divided in...AIM: To study the effect of mobilized peripheral blood autologous CD34 positive(CD34+) cell infusion in patients with non-viral decompensated cirrhosis.METHODS: Cirrhotic patients of non-viral etiology were divided into 2 groups based on their willingness to be listed for deceased donor liver transplant(DDLT)(control, n = 23) or to receive autologous CD34+ cell infusion through the hepatic artery(study group, n= 22). Patients in the study group were admitted to hospital and received granulocyte colony stimulating factor injections 520 μg/d for 3 consecutive days to mobilize CD34+ cells from the bone marrow. On day 4,leukapheresis was done and CD34+ cells were isolated using CliniMAC magnetic cell sorter. The isolated CD34+ cells were infused into the hepatic artery under radiological guidance. The patients were discharged within 48 h. The control group received standard of care treatment for liver cirrhosis and were worked up for DDLT as per protocol of the institute. Both groups were followed up every week for 4 wk and then every month for 3 mo.RESULTS: In the control and the study group, the cause of cirrhosis was cryptogenic in 18(78.2%) and16(72.72%) and alcohol related in 5(21.7%) and6(27.27%), respectively. The mean day 3 cell count(cells/μL) was 27.00 ± 20.43 with a viability of 81.84± 11.99%. and purity of 80%-90%. Primary end point analysis revealed that at 4 wk, the mean serum albumin in the study group increased significantly(2.83± 0.36 vs 2.43 ± 0.42, P = 0.001) when compared with controls. This improvement in albumin was,however, not sustained at 3 mo. However, at the end of3 mo there was a statistically significant improvement in serum creatinine in the study group(0.96 ± 0.33 vs 1.42 ± 0.70, P = 0.01) which translated into a significant improvement in the Model for End-Stage Liver Disease score(15.75 ± 5.13 vs 19.94 ± 6.68,P = 0.04). On statistical analysis of secondary end points, the transplant free survival at the end of 1 mo and 3 mo did not show any significant difference(P =0.60) when compared to the control group. There was no improvement in aspartate transaminase, alanine transaminase, and bilirubin at any point in the study population. There was no mortality benefit in the study group. The procedure was safe with no procedural or treatment related complications.CONCLUSION: Autologous CD 34+ cell infusion is safe and effectively improves liver function in the short term and may serve as a bridge to liver transplantation.展开更多
AIM: To enrich putative hepatic progenitors from the developing human fetal liver using CD34 as a marker. METHODS: Aborted fetuses of 13-20 wk were used for the isolation of liver cells. The cells were labeled with an...AIM: To enrich putative hepatic progenitors from the developing human fetal liver using CD34 as a marker. METHODS: Aborted fetuses of 13-20 wk were used for the isolation of liver cells. The cells were labeled with anti CD34; a marker used for isolating progenitor population and the cells were sorted using magnetic cell sorting. The positive fractions of cells were assessed for specific hepatic markers. Further, these cells were cultured in vitro for long term investigation. RESULTS: Flow cytometric and immunocytochemical analysis for alphafetoprotein (AFP) showed that the majority of the enriched CD34 positive cells were positive for AFP. Furthermore, these enriched cells proliferated in the long term and maintained hepatic characteristics in in vitro culture. CONCLUSION: The study shows that aborted human fetal liver is a potential source for isolation of hepatic progenitors for clinical applications. The study also demonstrates that CD34 can be a good marker for the enrichment of progenitor populations.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 Accurate preoperative staging of gastric cancer(GC),a common malignant tumor worldwide,is critical for appropriate treatment plans and prognosis.Dynamic three-phase enhanced computed tomography(CT)scanning for preoperative staging of GC has limitations in evaluating tumor angiogenesis.CD34,a marker on vascular endothelial cell surfaces,is promising in evaluating tumor angiogenesis.We explored the value of their combination for preoperative staging of GC to improve the efficacy and prognosis of patients with GC.Medical records of 106 patients with GC treated at the First People's Hospital of Lianyungang between February 2021 and January 2023 were retrospectively studied.All patients underwent three-phase dynamic contrast-enhanced CT scanning before surgery,and CD34 was detected in gastroscopic biopsy specimens.Using surgical and pathological results as the gold standard,the diagnostic results of three-phase dynamic contrast-enhanced CT scanning at different T and N stages were analyzed,and the expression of CD34-marked microvessel density(MVD)at different T and N stages was determined.The specificity and sensitivity of three-phase dynamic contrast-enhanced CT and CD34 in T and N staging were calculated;those of the combined diagnosis of the two were evaluated in parallel.Independent factors affecting lymph node metastasis were analyzed using multiple logistic regression.RESULTS The accuracy of three-phase dynamic contrast-enhanced CT scanning in diagnosing stages T1,T2,T3 and T4 were 68.00%,75.00%,79.41%,and 73.68%,respectively,and for diagnosing stages N0,N1,N2,and N3 were 75.68%,74.07%,85.00%,and 77.27%,respectively.CD34-marked MVD expression increased with increasing T and N stages.Specificity and sensitivity of three-phase dynamic contrast-enhanced CT in T staging were 86.79%and 88.68%;for N staging,89.06%and 92.86%;for CD34 in T staging,64.15%and 88.68%;and for CD34 in N staging,84.38%and 78.57%,respectively.Specificity and sensitivity of joint diagnosis in T staging were 55.68%and 98.72%,and N staging were 75.15%and 98.47%,respectively,with the area under the curve for diagnosis improving accordingly.According to multivariate analysis,a longer tumor diameter,higher pathological T stage,lower differ-entiation degree,and higher expression of CD34-marked MVD were independent risk factors for lymph node metastasis in patients with GC.CONCLUSION With high accuracy in preoperatively determining the invasion depth and lymph node metastasis of GC,CD34 expression and three-phase dynamic contrast-enhanced CT can provide a reliable basis for surgical resection.
文摘CD34+ cells from human umbilical cord blood were purified by Dynal beads M-450 CD34 immunoselection system and cultured in the presence of various cytokines alone or in combination, including stem cell factor (SCF), interleukin-6 (IL-6) and erythropoietin (EPO). The results revealed that: (D In methylcellulose culture, the plating efficiencies of purified cord blood CD34+ cells were much different when stimulated by various cytokines. IL-6 alone had the lowest colo-ny yield, while the combination of SCF, IL-6 and EPO had the highest yield. ② In the suspension culture, IL-6 alone or IL-6 + EPO had little expanding effect on cord blood CD34+ celis, the other cytokine combinations could expand cord blood CD34+ celis at different Ievels. Among them, the combination of SCF, IL-6 and EPO had the maximal expanding effect on cord blood CD34+ celis, the number of progenitor celis peaked at day 21, about 29-fold increase and nucleated celis increased approximately 3676-fold at day 28. The expanding effect of
文摘AIM:To assess the utility of an autologous CD34 + and CD133 + stem cells infusion as a possible therapeutic modality in patients with end-stage liver diseases.METHODS:One hundred and forty patients with endstage liver diseases were randomized into two groups.Group 1,comprising 90 patients,received granulocyte colony stimulating factor for five days followed by autologous CD34 + and CD133 + stem cell infusion in the portal vein.Group 2,comprising 50 patients,received regular liver treatment only and served as a control group.RESULTS:Near normalization of liver enzymes and improvement in synthetic function were observed in 54.5% of the group 1 patients;13.6% of the patients showed stable states in the infused group.None of the patients in the control group showed improvement.No adverse effects were noted.CONCLUSION:Our data showed that a CD34 + and CD133 + stem cells infusion can be used as supportive treatment for end-stage liver disease with satisfactory tolerability.
基金Supported by Grants from Asian Healthcare Foundation
文摘AIM: To study the effect of mobilized peripheral blood autologous CD34 positive(CD34+) cell infusion in patients with non-viral decompensated cirrhosis.METHODS: Cirrhotic patients of non-viral etiology were divided into 2 groups based on their willingness to be listed for deceased donor liver transplant(DDLT)(control, n = 23) or to receive autologous CD34+ cell infusion through the hepatic artery(study group, n= 22). Patients in the study group were admitted to hospital and received granulocyte colony stimulating factor injections 520 μg/d for 3 consecutive days to mobilize CD34+ cells from the bone marrow. On day 4,leukapheresis was done and CD34+ cells were isolated using CliniMAC magnetic cell sorter. The isolated CD34+ cells were infused into the hepatic artery under radiological guidance. The patients were discharged within 48 h. The control group received standard of care treatment for liver cirrhosis and were worked up for DDLT as per protocol of the institute. Both groups were followed up every week for 4 wk and then every month for 3 mo.RESULTS: In the control and the study group, the cause of cirrhosis was cryptogenic in 18(78.2%) and16(72.72%) and alcohol related in 5(21.7%) and6(27.27%), respectively. The mean day 3 cell count(cells/μL) was 27.00 ± 20.43 with a viability of 81.84± 11.99%. and purity of 80%-90%. Primary end point analysis revealed that at 4 wk, the mean serum albumin in the study group increased significantly(2.83± 0.36 vs 2.43 ± 0.42, P = 0.001) when compared with controls. This improvement in albumin was,however, not sustained at 3 mo. However, at the end of3 mo there was a statistically significant improvement in serum creatinine in the study group(0.96 ± 0.33 vs 1.42 ± 0.70, P = 0.01) which translated into a significant improvement in the Model for End-Stage Liver Disease score(15.75 ± 5.13 vs 19.94 ± 6.68,P = 0.04). On statistical analysis of secondary end points, the transplant free survival at the end of 1 mo and 3 mo did not show any significant difference(P =0.60) when compared to the control group. There was no improvement in aspartate transaminase, alanine transaminase, and bilirubin at any point in the study population. There was no mortality benefit in the study group. The procedure was safe with no procedural or treatment related complications.CONCLUSION: Autologous CD 34+ cell infusion is safe and effectively improves liver function in the short term and may serve as a bridge to liver transplantation.
基金Supported by Department of Biotechnology, Government of India
文摘AIM: To enrich putative hepatic progenitors from the developing human fetal liver using CD34 as a marker. METHODS: Aborted fetuses of 13-20 wk were used for the isolation of liver cells. The cells were labeled with anti CD34; a marker used for isolating progenitor population and the cells were sorted using magnetic cell sorting. The positive fractions of cells were assessed for specific hepatic markers. Further, these cells were cultured in vitro for long term investigation. RESULTS: Flow cytometric and immunocytochemical analysis for alphafetoprotein (AFP) showed that the majority of the enriched CD34 positive cells were positive for AFP. Furthermore, these enriched cells proliferated in the long term and maintained hepatic characteristics in in vitro culture. CONCLUSION: The study shows that aborted human fetal liver is a potential source for isolation of hepatic progenitors for clinical applications. The study also demonstrates that CD34 can be a good marker for the enrichment of progenitor populations.
