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Objective To assess the efficacy and safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) primed donor peripheral blood stem cell (PBSC) on the treatment of poor graft function (PGF) after allogeneic stem cell transplantation(allo-HSCT).Methods The patients diagnosed as PGF after allo-HSCT and transfused with rhG-CSF primed PBSC from January 2003 to November 2012 were retrospectively analyzed.Hematological response was assessed at day 30 after transfusion.Graft versus host disease (GVHD) was assessed until 6 months after transfusion.Results There were 28 patients including 21 men and 7 women with a median age of 28 (12-50) years old.Of these patients,16 were diagnosed as primary PGF.The median number of transfused mononuclear cells was 2.0 (1.0-5.8) ×108/kg.Totally 42.9％ (12/28) patients achieved good response.Eight patients (28.6％) developed GVHD.Sixteen patients (57.1％) survived.Age (≤/＞ 28 years),gender,donor type (matched sibling/mismatched related),additional conditioning regimen prior to transfusion,time of neutrophil engraftment (≤/＞ 18 days) time of transfusion (≤/＞ 100 days after allo-HSCT) and number of mononuclear cells (≤/＞ 2.0 × 108/kg) did not impact hematological response.However,response rate of primary PGF (4/16) was significantly lower than that of secondary PGF (8/12) (P =0.022).Conclusion Transfusion of PBSC mobilized by rhG-CSF could be considered as an option to treat secondary PGF after allogeneic stem cell transplantation.
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Objective To explore the effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) mobilization on TH17/Treg cells and its impact on suppressor of cytokine signaling-3 (SOCS3) gene expression in CD4+ T cells in donors' peripheral blood.Method Sixteen donors were injected subcutaneously with rhG-CSF 5 μg/kg every day for 5 consecutive days for peripheral blood stem cells mobilization.At the first 0,3,5 day,the mononuclear cclls (MNCs) in peripheral blood or graft and serum specimens were taken.The CD4 + T cells in MNCs were sorted using immuno-magnetic beads.The ratio of TH 17 and Treg cells in MNCs,cytokines concentrations of IL-17A,IL-21,ID23 and TGFβ1 in serum,and SODC3 gene expression in CD4+ T cells were detected by using flow cytometry,ELISA,and reverse transcription real-time quantitative PCR (RT-qPCR),respectively.Results (1)The ratio of Th17 cells (CD3+ CD8 CD17+) and Treg cells (CD4+ CD25+ Foxp3+) in MNCs in peripheral blood and graft at the first 0,3 and 5 days after mobilization was (2.69 ± 0.81) ％,(0.91 ± 0.33) ％,(0.35 ± 0.12) ％,(0.21 ± 0.05) ％,and (0.56 ± 0.24) ％,(0.72 ± 0.22％),(1.59 ± 0.54) ％,(3.38 ± 0.52) ％,respectively,showing a significant declining and increasing trend respectively (P＜0.05); (2)The cytokine concentrations in serum at the first 0,3 and 5 days after mobilization were 7.33 ± 0.89,5.78 ± 1.03 and 3.32 ± 0.84 μg/L for IL-17A; 124.56 ± 15.18,117.12 ± 14.45 and 64.94 ± 11.25 μg/L for IL-21 ; 183.52 ± 59.35,280.49 ± 69.75 and 393.62 ± 57.25μg/L for TGF-β1 (P＜0.01) ; and 45.89 ± 6.95,46.25 ± 7.44 and 47.45 ± 10.75 μg/L for IL-23,respectively.The IL-17A and IL-21 concentrations showed significant declining trend,contrarily TGF-β1 with an increasing trend,while IL-23 concentration had no change.After rhG-CSF mobilization,the SOCS3 gene expression in CD4 + T cells of peripheral blood and graft at the first 0,3,5 days was gradually increased.Conclusion rhG-CSF suppresses Th17 cells and promotes regulatory T cells generation,meanwhile decreases IL-17A and IL-21 and elevates serum TGF-β1 concentrations,and contributes to CD4 + T cells differentiation to Tregs,probably by elevating SOSC3 gene expression in CD4+ T cells.
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Objective To investigate the effects of rhG-CSF on the improvement of cognitive impairment and anti-apoptosis of Alzheimer disease (AD) induced by Aβ1-42 in rat. Methods Healthy male Wistarirats were randomly assigned to the Aβ group, treatment group and sham operation group. Aβ1-42 (10μg) was injected into bilateral hippocampus to create the rat model of AD. Rats in rhG-CSF group were subcutaneously subjected to 50μg/(kg · d) rhG-CSF for 5 days, while rats in Aβ group were subjected to normal saline. Morris water maze tests were done and expressions of caspase-3 protein were determined by immunohistochemical method on the 7th, 14th, 21st, and 28th day after administration. Results (1) The avoiding latent periods of rhG-CSF group ( ( 34. 33 ±6. 47 ) s, (42. 08 ± 6. 36 ) s, (46. 88 ± 7. 66 ) s, respectively ) were shorter than that of Ap group ((49.79 ±4.87)s, (50.25 ±6.81 )s, (51. 33 ±6.90)s, respectively). The percentages of swimming distances in the target quadrant in rhG-CSF group ( (41.00 ±7.62)% ,(43.33 ±8. 16)% ,(44. 67 ±8.07)% ,respectively) were increased comparing with Ap group((25.33 ±6.89)% , (23. 83 ±4.67)% ,(21.50 ±4.64)% ,respectively). The differences were all statistically significant (P<0.05). (2) Compared with sham operation group,the positive rate of caspase-3 protein in rat's hippocampus of Ap group significantly increased after injecting Aβ1-42 The positive rates of caspase-3 protein in rhG-CSF group on the 7th, 14th day ( (7. 93 ±6. 33) and (8. 83 ±5. 94) were lower than Aβ group ( ( 10.43 ±7. 16) and ( 11. 34 ± 5. 17 ) . The differences were statistically significant (P< 0.05). Conclusion RhG-CSF can improve the cognitive impairment of Alzheimer Disease (AD) induced by Aβ1-42 in rat, decrease the apoptosis of hippocampal neurons and delay the decline of its learning and memory ability to some extent.
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Mobilização inadequada de células progenitoras hematopoéticas (CPH) tem sido observada em 10 - 30% dos pacientes submetidos a transplante de medula óssea (TMO) autogênico para tratamento de doenças onco-hematológicas. Os fatores relacionados com má resposta à mobilização ainda não estão totalmente estabelecidos. Apresentamos uma análise retrospectiva de pacientes submetidos à TMO autogênico com o objetivo de identificar variáveis associadas com resposta ruim ao regime de mobilização utilizado. Casuística e Métodos: Fizeram parte desta análise 307 pacientes com diferentes diagnósticos, tratados com TMO autogênico em uma única Instituição, no período de Abril de 2001 a Abril de 2007. Todos os pacientes incluídos no estudo foram submetidos a um único regime de mobilização baseado na administração de ciclofosfamida (dose total de 60-120 mg/kg de peso IV) e fator estimulador de colônias de granulócitos (G-CSF) (dose diária de 6 - 17 ug/(kg de peso)/dia SC). O sucesso na resposta ao regime de mobilização foi definido quando um número maior ou igual a 2,0x10 (6) células CD34 + /(kg de peso) foi coletado do sangue periférico com até três procedimentos de leucaférese. Resultados: Dos pacientes analisados, 260 apresentaram sucesso na mobilização (84,7%). Nestes pacientes, um número mediano de 3,67 (2,0 - 46,0) células CD34+ /(kg de peso) foi coletado por paciente com um número mediano de 1 (1-3) procedimento de leucaférese. O insucesso na mobilização foi observado em 47 pacientes (15,3%): 24 (7,8%) que foram submetidos à coleta de CPH de sangue periférico, porém não coletaram número maior ou igual 2,0x10 (6) células CD34+/(kg de peso) com pelo menos três procedimentos de leucaférese; e, 23 (7,5%) foram submetidos à coleta de CPH por punção da medula óssea, por não terem atingido número mínimo de 10 células CD34+/mm3 no sangue periférico para realização de leucaférese...
Inadequate stem cells mobilization is seen in 10-30% of patients undergoing autotransplantation for hematologic malignancies. Factors affecting peripheral blood progenitor cell (PBSC) mobilization have not been clearly established. We retrospectively reviewed the data of patients treated by autologous bone marrow transplantation (BMT) with the aim to identify factors associated with poor PBSC mobilization. Design and Methods: We evaluated 307 patients with different diagnoses, submitted to autologous BMT between April 2001 and April 2007. PBSC were collected following mobilization with cyclophosphamide (60-120 mg/kg of weight IV) and granulocyte-colony stimulating factor (G-CSF) (dose of 6-17 ug/kg of weight/day SC). Success in mobilization was defined when > ou = a 2,0x10(6) CD34+ cells/(kg weight) could be collected from the peripheral blood with a maximum of three leukapheresis procedures. Clinical and laboratory parameters at the time of mobilization were analyzed for correlations with the number of CD34+ cells collected. Results: Two hundred and sixty patients (84.7%) presented success in mobilization. In this group, a median of 3.67 (2.0-46.0) CD34+ cells/(kg weight) was collected per patient in a median of 1(1-3) leukapheresis procedure. Poor response to mobilization was observed in 47 patients (15.3%): 24 (7.8%) were submitted to PBSC collection but didn't collected at least 2.0 x 106 CD34+ cells/(kg weight) with three leukapheresis procedures and 23 (7.5%) didn't reach an absolute number count of 10 CD34+ cells/mm3 in the peripheral blood to start collection by leukapheresis. In univariate analysis poorer PBSC mobilization was associated with diagnosis (Pp < 0.0001), time interval from the diagnosis to mobilization (P < 0.0001), number of cycles of previous chemotherapy (P = 0.0001), previous treatment with alkylating agents (P = 0.0003) and mitoxantrone (P = 0.0006), platelet count <150.000/mm3 before mobilization (P = 0.0006) and interval...
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Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Persona de Mediana Edad , Médula Ósea , Factor Estimulante de Colonias de Granulocitos , Movilización de Célula Madre Hematopoyética , Trasplante AutólogoRESUMEN
Objective To investigate the effects on proliferation of bone marrow mesenchymal stem cells (MSCs) by recombinant human granulocyte colony-stimulating factor in mice. Methods Kunming mice were randomly divided into G-CSF and control groups (n=15). The mice were subjected to subcutaneous injections of rhG-CSF at a dose of 80 ?g/kg per day and control of saline for 5 days. The bone marrow was obtained on 6th, 12th and 168th h respectively after the final administration. The MSCs were separated and cultured, and the colony-forming unit-fibroblast (CFU-F) was evaluated. The cell cycle and the surface antigens were analyzed by flow cytometry. Results The number of CFU-F was increased after administration of the rhG-CSF (P 0.05). Flow cytometic detection of MSCs surface marks in fibroblast colony showed CD34~ -, CD133~ -, CD90~ + and CD105~ +, with the percentage of 2.5 %, 3.1 %, 67.0 % and 78.0 %, respectively. After mobilization with rhG-CSF, the percentage of G_0/G_1 phases in bone marrow MNCs was decreased (P
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To explore the effect of recombinant human interleukin 11(rhIL-11), granulocyte-colony stimulating factor (rhG-CSF) combined with cyclophosphamide (CTX) on mobilizing peripheral blood stem/progenitor cells in C57BL/6 mice. A total of 48 C57BL/6 mice were randomized into four groups. CTX (200mg/kg) was injected intraperitonealy on the first day (d0) in the treatment group. rhIL-11 alone or in combination with rhG-CSF was administered subcutaneously, beginning from 24 hours after CTX for 15 consecutive days in two other groups. The changes in peripheral blood white cell counts, platelet counts and the percentage of hematopoietic stem/progenitor cells of the mice were observed. It was shown that rhIL-11 or/and rhG-CSF could increase the numbers of WBC, PLT, CFU-GM, CFU-E, CFU-MK progenitor cells, and the percentage of CD34 positive cells in peripheral blood of myelosupressed mice. The results demonstrated that rhIL-11 alone or in combination with G-CSF and CTX could mobilize bone marrow haematopoietic stem/progenitor cells into peripheral blood.
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To evaluate the effects of combined therapy of rhIL 11 and rhG CSF on monkeys irradiated with 8 0 Gy 60 Co ? ray. Animals were divided into control ( n =4) and rhIL 11+rhG CSF treatment group ( n =4). After irradiation the control was given no treatment, while the treatment group was given rhIL 11 50?g/(kg.d)+rhG CSF 10?g/(kg.d) and other symptomatic supportive treatment whenever needed. The results showed that all animals underwent nausea, diarrhea and fever. After irradiation, all blood cells in peripheral blood of the animals declined in quantity rapidly. Animals of the control died of hemorrhage and infection. Their mean surviving time after ? ray exposure was 18 2 days. Aninals of the treatment group all survived on the 45th day after exposure. Their peripheral blood cell counts recovered to near baseline level. Histopathological observation revealed that bone marrow cells of treated animals proliferated actively. The results suggested that a combination of rhIL 11 and rhG CSF treatment was significantly effective in extremely severe hematopoietic acute radiation sickness.
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AIM: To explore whether the administration of rhG-CSF improve the neurological function after focal cerebral ischemia and observe the expression of fibronectin. METHODS: Injection of 10 ?g?kg -1?d -1 rhG-CSF for 5 days was given subcutaneously to rats undergoing middle cerebral artery occlusion (MCAO). Neurological severity scores (NSS) test was performed. The expression of fibronectin and Brdu were observed by immunohistochemistry. To visualize the cellular colocalization of Brdu and fibronectin, glial fibrillary acidic protein (GFAP) and fibronectin, double fluorescent staining were used. RESULTS: ① NSS at 7th day, 14th day and 21th day of groups undergoing MCAO treated with rhG-CSF were 4.00?0.89, 3.83?1.17, 3.50?1.38, respectively. NSS at 7th day, 14th day and 21th day of the control groups undergoing MCAO were 5.50?1.38, 5.83?1.47,5.66?1.63, respectively. NSS of the treated groups were significantly lower than that of the control groups (P
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Objective To evaluate the therapeutic effects of combined recombinant human IL-11(rhIL-11) and recombinant human G-CSF (rhG-CSF) on the neutron-irradiated dogs. Methods 18 male beagle dogs were divided into radiation control group (C, n=7), symptomatic treatment group (S, n=4), and combination therapy group (T, n=7). All dogs were exposed to total body 2Gy 90% neutron radiation. From the first day after radiation, the animals of group T received rhG-CSF 10?g/(kg?d) and rhIL-11 50?g/(kg?d) subeutaneously for 14d and 21d respectively. The cell counts of peripheral blood and CFU-GM of bone marrow were carried out. Results All animals of group S and T survived, however, the survival rate of group C was only 57%. The cellcounts of T group peripheral blood cells (white blood cell at any time point , the platelet and red blood cell of recovery phase) were higher than that of C or S group. The count of T group bone marrow CFU-GM was 6 fold higher than that of group C or S on day 1, and still 1.75, 1.46 fold higher than that group C or S, respectively, on day 33. Conclusion the combination therapy of rhIL-11 and rhG-CSF significantly raised the white cell and platelet counts in ARS dogs induced by neutron irradiation by accelerating the recovery of bone marrow hematopoietic function.