Establishment of AML Mouse Model by Transplantation of Hematopoietic Cells from MLL-AF9 Transgenic Mice / 中国实验血液学杂志

OBJECTIVE@#To establish a leukemia mouse model induced by transplantation of hematopoietic cells from mixed lineage leukemia (MLL)-AF9 transgenic mice so as to provide the basis for the mechanism research and drug screening of acute myeloid leukemia (AML).@*METHODS@#MLL-AF9 knock-in mice were bred and identified. When the mice developed leukemia, white blood cell (WBC) count in peripheral blood, flow cytometry and morphology method were analyzed to identify the disease. When the WBC count in peripheral blood was more than 100×10@*RESULTS@#The natural onset times of leukemia on MLL-AF9 knock-in mice were 22-28 weeks. The spleens of the transgenic mice enlarged and the bone marrow showed the immature forms of myeloid leukemia cells. Both the bone marrow and spleen cells highly expressed myeloid markers, CD11b and Gr-1. At least 0.5×10@*CONCLUSION@#The leukemia model of hematopoietic cell transplantation based on MLL-AF9 transgenic mice is successfully established, which can be used for the study of the pathogenesis and evaluation of therapeutic effect of AML.

Fluacrypyrim induced apoptosis in acute myeloid leukemia cell lines / 国际药学研究杂志

Objective To investigate the effect of fluacrypyrim on the induction of apoptosis in human acute myeloid leuke-mia(AML)cell lines,NB4,THP-1 and HL-60,and explore the related mechanisms.Methods Trypan blue dye exclusion assay was used to estimate the growth of NB4,THP-1,and HL-60 cells after treatment with various concentrations of fluacrypyrim(1.25, 2.5,5 and 7.5 μmol/L)for 72 h.Cell apoptosis was evaluated by AnnexinⅤ-FITC/PI double stainning for the NB4 and THP-1 cells treated with fluacrypyrim(1.25,2.5 and 5 μmol/L)for 48 h as well as the HL-60 cells treated with fluacrypyrim(2.5,5 and 7.5 μmol/L) for 72 h.Western blotting was used to examine the protein expression of apoptotic regulators Bax,Mcl-1 and Caspase 3 in the NB4 cells treated with fluacrypyrim(1.25,2.5 and 5 μmol/L)for 24 h.Then,NB4 Cells were pretreated with Caspases inhibitor benzyloxy-carbonyl-Val-Ala-Asp-fluoromethylketone(Z-VAD-FMK)and exposed to fluacrypyrim at 2.5 μmol/L for 24 h,which was then evaluat-ed for the apoptosis using AnnexinⅤ-FITC/PI double stainning.Western blotting was used to examine the expression of the phosphory-lated and total proteins of mitogen-activated protein kinase(MAPK)signaling molecules,ERK,JNK and P38,in the NB4 cells treat-ed with fluacrypyrim(1.25,2.5 and 5 μmol/L)for 24 h. NB4 Cells were pretreated with ERK inhibitor U0126,JNK inhibitor SP600125,or P38 inhibitor SB203580 for 1 h and then exposed to fluacrypyrim at 2.5 μmol/L for 24 h,which was then analyzed for the apoptosis by the AnnexinⅤ-FITC/PI double stainning.Results The proliferation of NB4,THP-1 and HL-60 cells was inhibited by the treatment with fluacrypyrim(2.5,5 and 7.5 μmol/L)for 72 h.The apoptosis induced in the NB4 and THP-1 cells by the fluacry-pyrim treatment at 5 μmol/L for 48 h and in the HL-60 cells by the fluacrypyrim treatment at 7.5 μmol/L for 72 h were significant as compared with the control group(P<0.01).Mechanically,fluacrypyrim at the concentrations of 2.5 and 5 μmol/L effectively up-regu-lated the expression of Bax(P<0.01 and P<0.05)for the 2.5 and 5 μmol/L,respectively,down-regulated the expression of Mcl-1 (P<0.01)and activated Caspase 3(P<0.01)in the NB4 cells when compared with the control group(P<0.01).The pretreatment of the NB4 cells with Z-VAD-FMK blocked the apoptosis induced by fluacrypyrim.Furthermore,the fluacrypyrim(2.5 and 5 μmol/L) treatment increased the ERK,JNK and P38 phosphorylation(P<0.01),while the pretreatment of the NB4 cells with U0126 signifi-cantly inhibited the the fluacrypyrim-induced apoptosis(P<0.01),as compared with the control group.Conclusion Fluacrypyrim effectively inhibits the cell proliferation and induces caspase-dependent cell apoptosis in AML cells.Activation of ERK/MAPK signal-ing pathway might play an important role in the action of fluacrypyrim.

Therapeutic Effect of Recombinant Human Stem Cell Factor on Rhesus Monkeys with Severe Acute Radiation Sickness / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the therapeutic effect of rhSCF early administration on rhesus monkeys with severe acute radiation sickness(ARS).</p><p><b>METHODS</b>Twelve adult monkeys totally exposed to 7.0 GyCo were divided into radiation control and SCF groups, and monkeys in SCF group were subcutaneously injected recombinant human SCF(rhSCF) 200 µg/kg at half an hour and 24 hour after irradiation, while the radiation control monkeys were injected physiological saline. Survival was monitored and hematopoiesis was evaluated at 40 days following early treatment.</p><p><b>RESULTS</b>6 animals treated with rhSCF all survived, while 2 in irradiated controls survived on 40 day after radiation. rhSCF treatment promoted hematopoiesis recovery significantly, increased the nadir of white blood cells, neutrophils and platelets, and simplified supportive care in ARS rhesus monkeys.</p><p><b>CONCLUSION</b>RhSCF injection soon after TBI taken shows an significant therapeutic efficiency on rhesus monkeys with severe acute radiation sickness.</p>

Therapeutic Effect of Combined Cytokines on Nonhuman Primate Model of Severe Haemopoietic Acute Radiation Sickness / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effects of combined administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-2 (rhIL-2) on radiation-induced severe haemopoietic acute radiation sickness (ARS) in rhesus monkeys, so as to provide experimental evidences for the effective clinical treatment.</p><p><b>METHODS</b>Seventeen rhesus monkeys were exposed to 7.0 Gy (60)Co γ-ray total body irradiation (TBI) to establish severe haemopoietic ARS model, and were randomly divided into supportive care group, rhG-CSF+rhTPO treatment group and rhG-CSF+rhTPO+rhIL-2 treatment group. Survival time, general signs such as bleeding and infections, and peripheral blood cell counts in each group were monitored. Bone marrow cells were cultivated to examine the colony formation ability. The histomorphology changes of bone marrow were observed at 45 d post irradiation.</p><p><b>RESULTS</b>After 7.0 Gy (60)Co γ-ray TBI, monkeys of supportive care group underwent tarry stool and emesis, then died in 12~18 d. The overall survival rate in this group was 16.7%. Gastrointestinal reactions of monkeys in two combined-cytokines treatment groups were inapparent. Combined-cytokines treatment induced 100% survival. Complete blood cells declined sharply after irradiation in each group, but two combined-cytokines treatment schemes could elevate the nadir of all blood cells, shorten the duration of pancytopenia and accelerate the recovery of hemogram. Compared with rhG-CSF+ rhTPO treatment, rhG-CSF+ rhTPO+ rhIL-2 treatment could increase the counts of lymphocytes and monocytes. The colony-formation rate of haemopoietic stem/progenitor cells in bone marrow dropped markedly at 2 d after irradiation. Combined-cytokines treatment promoted the ability of colony formation on day 29. Hematopoietic cells mostly disappeared in bone marrow of animals in supportive care group, but hematopoietic functions were recovered after cytokines were administrated.</p><p><b>CONCLUSION</b>rhG-CSF+ rhTPO and rhG-CSF+ rhTPO+ rhIL-2 treatment can significantly promote hematopoiesis recovery, improve the quantity of life, simplify the supportive therapy, and enhance the survival rate of rhesus monkeys with severe haemopoietic ARS induced by 7.0 Gy (60)Co γ-ray exposure. Especially the application of rhIL-2 can accelerate the recovery of lymphocytes and monocytes and restore the immunological function. Thus, combination of rhG-CSF, rhTPO and rhIL-2 on the basis of supportive care is an efficient strategy to treat severe haemopoietic ARS.</p>

Effects of HS 6101 and rhG-CSF on Hematopoiesis Recovery of ICR Mice Injured by Cyclophosphamide / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of HS 6101 and recombinant human granulocyte colony stimulating factor (rhG-CSF) on hematopoiesis recovery of ICR mice injured by cyclophosphamide (CTX).</p><p><b>METHODS</b>A total of 103 ICR mice were divided into 4 groups, including CTX control (46 mice), HS 6101 (21 mice), rhG-CSF (18 mice) and HS 6101+rhG-CSF (18 mice), respectively. The mouse model of chemotherapy-induced haematopoietic injury was established by CTX intraperitoneal injection at a dose of 100 mg/kg once a day for 3 consecutive days. Single dose of HS 6101 (27 µg/mouse) was injected subcutaneously at 1 hour before the first administration of CTX. One day after the last CTX treatment, 2 µg/mouse of rhG-CSF was injected subcutaneously once a day for 5 consecutive days. The peripheral blood cell counts of the mice were observed once every 2 days. Hematopoietic progenitor cell colony counting and histopathological assessment of bone marrow cells were evaluated in the mice at days 4 and 9 after the first administration of CTX.</p><p><b>RESULTS</b>Both HS 6101 and rhG-CSF alone or in combination, significantly elevated the nadirs of peripheral blood leukocytes and neutrophils, increased the number of bone marrow hematopoietic progenitor cells, and stimulated the hematopoietic cell hyperplasia of bone marrow in the mice treated with CTX. The effect of HS 6101 combined with rhG-CSF was better than that of the drugs used alone.</p><p><b>CONCLUSION</b>The HS 6101 at 27 µg/mouse can significantly promote the recovery of hematopoiesis in ICR mice treated with CTX chemotherapy, and its combination with rhG-CSF shows synergistic effects.</p>

Mobilization Effect of HS6101 on Hematopoietic Cells of Mice / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was aimed to investigate the mobilization effect of HS6101 on hematopoietic cells of mice.</p><p><b>METHODS</b>The normal ICR mice were injected subcutaneously once or twice with HS6101 at 9 µg/d/mouse, or a single dose of HS6101 3, 9, 27 and 81 µg/mouse was administrated, and the mobilization effect of HS6101 in different administration times and different dosage was observed, and compared with the synergistic effects of administration of single dose of HS6101 combined with rhG-CSF (2 µg/d/mouse was injected subcutaneously for 5 consecutive days). The peripheral blood cell counts of mice were detected at different time after administration. The hematopoietic stem/progenitor cells of bone marrow and peripheral blood were detected at day 5 and 10 after administration.</p><p><b>RESULTS</b>There was no significant difference in peripheral blood cell counts after once or twice injections of HS6101 9 µg/mouse. The peripheral platelet counts dose-dependently increased in ICR mice, which accounted for 121.1% to 118.0%, 138.7% to 123.1%, 146.4% to 139.2%, and 156.2% to 168.7% (P < 0.001) after HS6101 (3, 9, 27 and 81 µg/mouse) treatments at 5 and 7 d, respectively. HS6101 (3, 9, 27 and 81 µg/mouse) showed dose-response relationship to platelets, with R value of 0.777 and 0.954 at day 5 and 7 after administration, respectively. HS6101 significantly increased numbers of hematopoietic stem/progenitor cells in both bone marrow and peripheral blood, and elevated peripheral blood leukocytes at 27 µg/mouse dose at day 5 after administration.</p><p><b>CONCLUSION</b>HS6101 has significant mobilization effect on hematopoietic stem/progenitor cells, platelets and leukocytes in mouse.</p>

Effects of Different Dose of Cyclophosphamide on Peripheral Blood Cells of Normal ICR Mice / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate effective doses of cyclophosphamide (CTX) for establishment of leukopenia model in ICR mouse.</p><p><b>METHODS</b>Normal ICR mice (n = 96) were divided into CTX(80), CTX(100), CTX(120), CTX(150) and CTX(300) groups, of which mice received CTX intraperitoneally at a dose of 80, 100, 120, or 150 mg/kg once a day for 3 consecutive days, or 300 mg/kg with single injection. The peripheral blood cell counts were detected at various times before and after CTX administration.</p><p><b>RESULTS</b>The peripheral white blood cell nadirs in the mice injected with CTX appeared on day 4 after the first dose of CTX. The peripheral white blood cell nadir in group CTX(100) was 26.7% of the value measured in mice before CTX administrated, and that of group CTX(80) was 35.0%. Higher doses of CTX, however, caused too severity in hematopoietic injury.</p><p><b>CONCLUSION</b>The dose of CTX 100 mg/(kg·d) × 3d is appropriate for leucopenia model of ICR mouse.</p>

Protective effect of HS-6101 on rhesus monkeys with severe hematopoietic acute radiation sickness / 中国实验血液学杂志

This study was purposed to investigate the protective effects of lipoprotein HS-6101(6101) on rhesus monkey total body irradiated with 7.0 Gy ⁶⁰Coγ-ray. A total of 30 health adult rhesus monkeys were randomly divided into symptomatic therapy (ST), WR2721 and HS-6101 30, 90 and 270 mg/kg groups (n = 6), the rhesus monkeys of each groups were injected with physiological saline 0.3 ml/kg, WR-2721 30 mg/kg, or HS-6101 30, 90 and 270 µg/kg, respectively. All agents were once intramuscularly injected at 1 hr prior irradiation. General observation, peripheral blood cell counts, colony forming unite assay of bone marrow hemopoietic progenitor cells, and histopathological examination were performed. The results showed that animals in symptomatic therapy group begin to die on the 13(th) day and 4 animals died within 24 days, the average survival time was 18.2 ± 4.3 days; 2 animals in WR-2717 groups died on day 15.8 and day 18.5 post irradiation respectively. 1 animal in HS-6101 270 mg/kg group died on day 35.8, all other animals survived. Nadirs of peripheral blood white blood cells, neutrophils and platelets of animals in HS-6101 treatment groups were significantly higher than those in other 2 groups including ST and WR-2721 groups, and the hemopoietic recovery were also significantly speeding up(P < 0.05 and 0.01). In vitro results showed that HS-6101 obviously promoted 7.0 Gy ⁶⁰Coγ irradiated monkey's bone marrow mononuclear cells to form various hematopoietic progenitor cell colonies (P < 0.05 and 0.01) . Compared with symptomatic therapy and WR-2717 groups, bone marrow histopathological changes in HS-6101 treatment groups showed more active hemopoietic cell proliferation and higher density structure. It is concluded that HS-6101 90 µg/kg treatment can promote the bone marrow recovery of 7.0 Gy ⁶⁰Coγ irradiated monkey, alleviate their animal symptom, simplify the treatment measures and improve the animal survival rate. The HS-6101 shows remarkable radioprotective effects as compared with the currently internationally acknowledged radioprotectant of WR-2721.

Effect of GW003 on the granulocyte macrophage colony formation ability of bone marrow cells in vitro / 中国实验血液学杂志

The aim of this study was to investigate the effect of GW003 on the ability of granulocyte colony forming in vitro of bone marrow cells. The bone marrow samples was collected from normal rhesus, the patients with leukemia in stages of remission and chemotherapy respectively, and the nucleated cells were separated and cultured for 12 days after addition of different concentrations of GW003 or rhG-CSF, or G-CSF mutant. Then the amount of colony-forming unit-granulocyte-macrophage was counted. The results indicated that GW003 could enhance the ability of bone marrow nucleated cells of rhesus to forming CFU-GM in vitro, and its effect was much better than that of rhG-CSF or G-CSF mutant at the same concentration(®). The GW003 showed dose-response relationship to CFU-GM level (r = R(2) = 0.965, P = 0.003, in a certain concentration), the GW003 also could enhance CFU-GM formation of marrow nucleated cells in leukemic patients, especially for patients receiving chemotherapy. The GW003 could relieve the marrow suppression caused by chemotherapy significantly. It is concluded that the GW003 can significantly improve the ability of bone marrow cells to form granulocyte colony in vitro as well as effectively alleviate bone marrow suppression.

Radiation protection effect of rhIL-12 on monkey hematopoietic system / 中国实验血液学杂志

This study was aimed to investigate the radioprotective effects of recombinant human interleukin-12 (rhIL-12) on monkey hematopoietic system, and to provide experimental evidence for future clinical prophylaxis and treatment for patients who suffered from acute radiation syndrome. In in vitro study, the effect of rhIL-12 in different concentrations (0, 1, 5, 25, 125 and 625 ng/ml) on colony forming capacity of human or monkey bone marrow-derived mononuclear cells was examined in methylcellulose H4434 medium. In in vivo study, the acute radiation syndrome model was established in 11 Rhesus monkeys which received lethal total body irradiation by 6 Gy (60)Co γ in single time irradiation. The irradiated monkeys were randomly divided into 3 subgroups: control group (n = 4) which received subcutaneous PBS injection, rhIL-12 single-dose group (n = 3) which received subcutaneous single injection of rhIL-12 (4 µg/kg) at 2 h after irradiation, and multiple-dose group (n = 4) which received subcutaneous injection of rhIL-12 (1 µg/kg per injection) at 2 h, day 3, 6 and 9 after irradiation respectively. Peripheral blood cells were counted before and after irradiation every other day. The survival status of animals were observed daily. In vitro test results showed that different concentrations of rhIL-12 obviously promoted human and healthy monkeys' bone marrow mononuclear cells to form various hematopoietic progenitor cell colonies, especial CFU-E and CFU-GM. All animals in control group died within 22 d after lethal total body irradiation, average survival time was (20.3 ± 1.2) d. Only one monkey in multiple-dose group died due to anemia on day 17. All monkeys in single-dose group survived. Compared with control group, rhIL-12-administrated monkeys' white blood cell count, hemoglobin level, platelet and reticulocyte counts showed faster recovery from high dose radiation. It is concluded that the rhIL-12 treatment can promote the bone marrow hematopoietic stem/progenitor cell colony formation in vitro and protect lethally-irradiated monkeys. There is an obvious therapeutic effect of rhIL-12 on monkeys suffered from bone marrow failure caused by severe acute radiation exposure.

Transfection of ECSOD to Rhesus bone marrow mesenchymal stem cells in vitro / 中国实验血液学杂志

This study was aimed to investigate the biological effects of Rhesus bone marrow mesenchymal stem cells (R-BMMSC) transfected by adenovirus bearing extracellular superoxide dismutase gene (AD-ECSOD). Using density gradient centrifugation and adherent culture way, the R-BMMSC transfected by AD-ECSOD and reporter gene EGFP were isolated, cultured and purified; the transfection efficiency was detected by fluorescence microscopy and flow cytometry; the ECSOD protein expression in cell culture supernatant were detected by ELISA; the surface antigens on R-BMMSC (CD34, CD29, CD45, CD90, HLA-DR) were detected by flow cytometry; and differentiation capability of transfected R-BMMSC were detected by oil red O and alizarin staining; the proliferation capability of R-BMMSC was assay by MTT method. The results showed that the transfection efficiency of AD-ECSOD (MOI 500, 1 000, 1 500 and 2 000) for R-BMMSC was > 95%. At 24 h after transfection, the ECSOD protein could be detected in cell culture supernatant, and its level was significantly higher than that of control group (P < 0.01). At 48 h after transfection, the expression level of ECSOD protein on MOI 1 500 and 2 000 was the highest. The proliferative capability, surface antigen expression and multi directive differentiation ability of transfected R-BMMSC were similar to non-transfected R-BMMSC. It is concluded that the AD-ECSOD can effectively transfect the R-BMMSC without influences on its biological features.

High dose granulocyte colony-stimulating factor enhances survival and hematopoietic reconstruction in canines irradiated by 2.3 Gy mixed fission neutron and gamma ray / 中国实验血液学杂志

This study was purposed to evaluate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on hematopoietic reconstruction and survival in beagles exposed to mixed fission neutron and γ-ray. 13 beagles were unilaterally exposed to single dose of 2.3 Gy 90% neutrons. The experiments were divided into 3 groups: irradiation control group (no any treatment, n = 4), supportive care group (n = 5) and rhG-CSF plus supportive care group (n = 4, abbreviated as rhG-CSF group) in which the beagles were subcutaneously injected with 200 µg/kg of rhG-CSF early at half an hour and 24 hours post-irradiation respectively. The results showed that 2.3 Gy 90% neutron irradiation induced a severe acute radiation sickness of bone marrow type. The administration of rhG-CSF increased the survival rate from 60% in supportive care group to 100%. Twice injection of rhG-CSF in the first 24 hours reduced duration of neutropenia, enhanced neutrophil nadir and promoted neutrophil recovery when compared with control cohort administered clinical support. The number of colony-forming cells (CFU-GM, CFU-E, and BFU-E) in peripheral blood of rhG-CSF treated canines increased 2-to 5-fold relative to those of the supportive care group on day 3. All canines treated with rhG-CSF achieved hematopoietic reconstruction as evidenced by the pathological section of sternum while severe shortage of hemopoietic cells remained in the cohorts given supportive care alone. It is concluded that the combination of supportive care and high-dose rhG-CSF can accelerate hematopoietic recovery and enhance survival of dogs exposed to 2.3 Gy mixed neutron and gamma ray.

Effect of rhG-CSF on blood coagulation in beagles irradiated by 2.3 Gy neutron / 中国实验血液学杂志

The aim of this study was to investigate the effect of recombinant human granulocyte stimulating factor (rhG-CSF) on blood coagulation of beagles irradiated by 2.3 Gy neutron so as to provide new therapy for blood coagulation disorder after neutron irradiation. 10 beagles were exposed to 2.3 Gy neutron, and then randomly assigned into supportive care group and rhG-CSF-treated group. The rhG-CSF-treated cohorts were injected subcutaneously with rhG-CSF (10 µg/kg·d) beginning at the day of exposure for 21 consecutive days. Peripheral blood platelet counts were examined once every two days. In vitro platelet aggregation test, thromboelastography and blood clotting tetrachoric tests were also performed. The results indicated that the blood clotting system of irradiated dogs was in hypercoagulable state in the early days after 2.3 Gy neutron irradiation, and became hypocoagulable at crisis later and were mainly on intrinsic coagulation pathway. Blood fibrinogen increased markedly during the course of disease, while platelet counts and aggregation function were decreased remarkably. rhG-CSF administered daily could correct hypercoagulable state induced by 2.3 Gy neutron irradiation at the early time post exposure, shortened the thromboplastin generation time and clotting formation, down-regulated the abnormal high fibrinogen in blood, and improved platelet aggregation function. It is concluded that rhG-CSF can improve coagulation disorders of irradiated dogs.

Expression of human HSF in E. coli and its effects on mobilization of hematopoietic stem cells in rhesus monkeys / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the expression of hHSF in E. coli and its effect on the mobilization of hematopoietic stem/progenitor cells.</p><p><b>METHODS</b>The hHSF gene was obtained by overlapping PCR and cloned into the vector pET30a to yield pET30a-hHSF, which was transformed into E. coli BL21(DE3) and expressed with IPTG induction. Subsequently, rhHSF was purified by gel filtration and cation exchange chromatography and subjected to refolding. Molecular weight of hHSF was measured by MALDI-TOF Mass Spectroscopy. The N terminal amino acid sequence rhHSF was determined by protein sequencing. rhHSF was profiled in rhesus monkey for mobilization of peripheral blood stem cells. Eight rhesus monkeys were equally divided into two groups. The first group was administered single subcutaneous injection of 500 microg/kg hHSF, while the other one was administered 10 microg.kg(-1).d(-1) G-CSF for 4 days followed by a single subcutaneous injection of 500 microg/kg rhHSF.</p><p><b>RESULTS</b>The sequence coding hHSF was confirmed by sequencing and the induced-expression level was about 30% of total cell proteins. The purity of target protein was over 95%. The sequence of N terminal 10 amino acids and the amino acid composition were consistent with the theoretical parameters; molecular weight of rhHSF was 7540. The peripheral CD34(+) cells, CFU-GM yields, and neutrophils peaked at 3 h (16.3-folds increase compared with baseline), 1 h (1.9-folds increase) and 45 min (4.4-folds increase) respectively after the single injection of rhHSF. The addition of rhHSF after the last dose of G-CSF boosted these levels to 25.8-folds, 8.7-folds and 8.3-folds respectively.</p><p><b>CONCLUSION</b>hHSF is highly expressed in E. coli and rapidly mobilizes the hematopoietic stem/progenitor cells and neutrophils in rhesus monkeys. hHSF shows distinct synergistic effect with G-CSF.</p>

The effects of rhG-CSF and rhSCF on peripheral blood leukocytes and CFU-GM in rhesus monkeys / 中国实验血液学杂志

To evaluate the effects of rhG-CSF and rhSCF on mobilization of the peripheral blood stem cells, 15 monkeys were divided into control, rhG-CSF 10 micro g/(kg x day) and rhG-CSF 10 micro g/(kg x day) + rhSCF 50 micro g/(kg x day) treated groups. Monkeys were administered with vehicle, rhG-CSF and rhG-CSF + rhSCF subcutaneously once daily for 14 days, respectively. The results showed that the highest counts of leukocyte of rhG-CSF treated group were 411% of baseline value on day 7 after administration, compared with that of rhG-CSF + rhSCF treated group which were 538% on day 9. The highest counts of leukocytes lasted for 3 days in combined treated group. CFU-GM from peripheral blood in the two groups were 8.37 and 11.75 times higher at 5 and 9 days respectively after the mobilization. It is concluded that rhG-CSF significantly increases the number of peripheral blood leukocytes and CFU-GM, and a better effect can be obtained by rhSCF + rhG-CSF combined administration.

Therapeutic Effects of rhIL-11 on Irradiation-Induced Myelosuppression in Rhesus Monkeys / 中国实验血液学杂志

The efficacy of rhIL-11 in treating thrombocytopenia and neutropenia in gamma-irradiated rhesus monkeys and the variation in curative effect due to difference of administration times were studied. Healthy rhesus monkeys were exposed to 3.0 Gy (60)Co total body irradiation (TBI) to result in pancytopenia for three weeks. Treatment with rhIL-11 (30, 60 or 120 micro g.kg(-1).day(-1)) on early days (days 0 - 13 after TBI) could significantly improve the nadir of platelet count. Although the nadir of leukocyte count was not improved, the duration below 50% of its baseline value was shortened similarly to that of platelet. During the first two weeks after TBI, erythrocyte numbers of the animals treated with these doses of rhIL-11 were lower than those of the control group at first but they became higher beginning from the third week. Four monkeys were treated with rhIL-11 at 60 micro g.kg(-1).day(-1) on days 13 - 26 after TBI. The numbers of their peripheral blood cells followed the similar decrease patterns as those of control group during the first three weeks, then they were improved rapidly. By semi-solid bone marrow cell culture it was demonstrated that rhIL-11 could stimulate bone marrow cells to form more CFU-Meg, CFU-Mix, CFU-E, BFU-E and CFU-GM in vitro. Histopathological observation revealed that bone marrow of the control group was devoid of hematopoietic cells and bleeding, being contrary to that of the group treated with rhIL-11, in which the cells proliferated actively. The results suggest that rhIL-11 can accelerate hematopoietic recovery of irradiated monkeys.