Mobilization of Peripheral Blood Stem Cells Using Regimen Combining Docetaxel with Granulocyte Colony-stimulating Factor in Breast Cancer Patients

Objective：To evaluate the effectiveness and safety of the mobilization of peripheral blood hematopoietic stem cells by combining docetaxel with granulocyte colony-stimulating factor（G-CSF） in breast cancer patients.Methods：A total of 57 breast cancer patients were treated with docetaxel 120 mg/m2.When the white blood cell（WBC） count decreased to 1.0×109/L,patients were given G-CSF 5-g/kg daily by subcutaneous injection until the end of apheresis.Peripheral blood mononuclear cells（MNC） were isolated by Cobe Spectra Apheresis System.The percentage of CD34＋ cell was assayed by flow cytometry.Results：At a median 6 of days（range 3-8） after the administration of docetaxel,the median WBC count decreased to 1.08×109/L（range 0.20-2.31）.The median duration of G-CSF mobilization was 3 days（range 2-7）.The MNC collection was conducted 8-12 days（median 10 days） after docetaxel treatment.The median MNC was 5.35×108/kg（range 0.59-14.07）,the median CD34＋ cell count was 2.43×106/kg（range 0.16-16.69）.The CD34＋ cell count was higher than 1.00×106/kg in 47 of 57 cases（82.46%） and higher than 2.00×106/kg in 36 cases（63.16%）.The CD34＋ cell count was higher than 2.00×106/kg in 27 collections（23.68%）.The MNC count and the CD34＋ cell count were correlated with the bottom of WBC after docetaxel chemotherapy（r=0.364,0.502,P=0.005,0.000）.The CD34＋ cell count was correlated with the MNC count（r=0.597,P=0.000）.The mobilization and apheresis were well tolerated in all patients.Mild perioral numbness and numbness of hand or feet were observed in 3 cases.No serious adverse events were reported.Conclusion：Mobilization of peripheral blood hematopoietic stem cell by combining docetaxel with G-CSF was effective and safety in breast cancer patients.

Neuroprotective Effect of Granulocyte Colony-stimulating Factor in a Focal Cerebral Ischemic Rat Model with Hyperlipidemia

Granulocyte colony-stimulating factor (G-CSF) has been demonstrated to have neuroprotective effects in rat model with focal cerebral ischemia through anti-apoptotic pathways and by promoting proliferation of neural stem cells. In the present study, we examined the neuroprotective effect of G-CSF in an acute focal cerebral ischemia rat model with lipid metabolism disorder. Eighty male SD rats were randomly divided into normal diet control group (NC group) and high-fat diet group (HFD group) (n = 40 in each). In HFD group, rats were fed on high fat diet to induce atherosclerosis. After 29 days, 4 rats from each group were sacrificed to evaluate the effects of different diets, and the middle cerebral artery occlusion (MCAO) was performed in the rest of the rats. MCAO rats received either G-CSF (50 μg·kg–1·mL–1) or phosphate buffered saline (PBS) injection through the external jugular vein for 5 days, which was followed by 5-bromo-deoxy uridine (BrdU, i.p., 50 mg/kg) injection for another 7 days. To evaluate the effects of G-CSF treatment on neurological function, the modified neurological severity score (mNSS) was calculated. The vascular distribution, ischemic cells proliferation, cell apoptosis and the expression of vascular endothelial growth factor (VEGF) were measured to determine the effects of G-CSF treatment. Our results showed that G-CSF-treated rats had a lower mNSS than PBS-treated rats in both NC group and HFD group. G-CSF injection promoted endothelial cell proliferation and vascular regeneration, and inhibited cell apoptosis. The serum and tissue levels of VEGF were significantly increased after G-CSF treatment. It is concluded that G-CSF exerts its neuroprotective effect in focal cerebral ischemia rats with hyperlipidemia by enhancing angiogenesis, promoting cells proliferation, decreasing cell apoptosis, and increasing local VEGF expression.

Granulocyte colony-stimulating factor-producing hepatocellular carcinoma with abrupt changes

Granulocyte colony-stimulating factor(G-CSF)-producing tumor is one of the rare types of cancer clinically characterized by an elevated fever and white blood cell(WBC) increment. Although G-CSF producing tumors have been reported in several types of cancer including those of the lungs, cervix and bladder, G-CSF producing hepatocellular carcinoma is extremely rare. Here, we report the case of a rapidly growing and poorly differentiated hepatocellular carcinoma producing G-CSF. The patient showed symptoms of continuous high fever, stomach pain and cough, and high serum WBC counts, C-reactive protein(CRP) and G-CSF levels were found in laboratory tests. After a radical hepatectomy, the patient completely recovered from the above symptoms and inflammatory state. The serum levels of G-CSF were reduced to normal levels after radical surgery. An immunohistochemical analysis revealed the overexpression of G-CSF in the cytoplasm of certain hepatocellular carcinoma(HCC) cell. The patient's serum WBC, CRP and G-CSF levels remained within normal levels in the six months after surgery without recurrence. This is the 9^(th) case report of G-CSF producing hepatocellular carcinoma in English literature. We review the clinical characteristics of the G-CSF producing HCC and discuss a possible treatment strategy.

Granulocyte colony-stimulating factor-producing squamous cell carcinoma of the tongue exhibiting characteristic fluorine-18 deoxyglucose accumulation on positron emission tomography–computed tomography: A case report

BACKGROUND Granulocyte colony-stimulating factor(G-CSF)is a cytokine produced in inflammatory environments that induces differentiation and proliferation of neutrophils in bone marrow.We report a rare case of aggressive G-CSFproducing squamous cell carcinoma of the tongue exhibiting fluorine-18 deoxyglucose(FDG)accumulation in primary lesion,metastatic lymph nodes,spleen,and bone marrow on positron emission tomography–computed tomography(PET/CT).CASE SUMMARY We report a 58-year-old female with a rapid enlarged lingual mass with partial necrosis.Blood test results from the initial examination revealed a leukocyte count of 21380/μL.On PET/CT,extensive FDG accumulation was observed in the tongue and bilateral cervical lymph nodes,with elevated FDG accumulation in the spleen and bone marrow although no distant metastases were observed.We performed partial glossectomy and bilateral neck dissection.Immunohistochemical staining with G-CSF antibodies on biopsy specimen and resected samples revealed that both specimens were G-CSF positive.This is a rare case of G-CSF producing tongue carcinoma with elevated FDG accumulation in the spleen and bone marrow.CONCLUSION In patients with the tongue cancer and hyperleukocytosis,where FDG accumulations in the spleen and bone marrow are observed using PET/CT and when these accumulations are not caused by metastasis,G-CSF-producing tumors,with associated poor prognosis,should be considered.

Granulocyte colony-stimulating factor increases extracellular glutamic acid uptake and suppresses free radicals in an experimental model of amyotrophic lateral sclerosis

Excitatory amino acid toxicity and free radical damage play important roles in amyotrophic lateral sclerosis. Granulocyte colony-stimulating factor （G-CSF） protects nerve cells exposed to high-concentrations of glutamic acid, suggesting positive effects in the treatment of amyotrophic lateral sclerosis. The present study induced in vitro motor neuron injury using glutamic acid excitotoxicity, and the biochemical effects of G-CSF on glutamic acid concentration were determined. In addition, the effects of G-CSF on superoxide dismutase, glutathione peroxidase activity in motor neurons, and malondialdehyde and nitric oxide contents were analyzed. Immunohistochemistry was performed to measure neuronal survival. Results revealed that G-CSF significantly suppressed free radical activity, inhibited excitotoxicity, and reduced apoptosis and loss of motor neurons in the anterior horn of the spinal cord.

Granulocyte colony-stimulating factor as a novel adjunct to improve hepatitis B vaccination

Hepatitis B vaccination is successful in 95% of individuals. In the remainder, despite repeated attempts, immunization often remains unsuccessful. 'Non-response' leaves the individual susceptible to infection. Various strategies have been employed to overcome this. These include the use of adjuncts alongside conventional vaccines which activate immune responses. In this case report we demonstrate the successful use of the hematopoietic growth factor Granulocyte colonystimulating factor (G-CSF) as a vaccine adjunct in an individual who had previously failed conventional vaccination three times. The patient tolerated the regimen without any side effects and achieved a hepatitis B surface antibody titer greater than 100 IU/L. Use of G-CSF as a vaccine adjunct for hepatitis B has not previously been reported and the outcome in this case suggests that the use of G-CSF in this context warrants further exploration.

Granulocyte colony-stimulating factor promotes growth of processes,growth associated protein 43 and microtubule-associated protein 2 expression in cultured rat retinal ganglion cells in vitro

Following granulocyte colony-stimulating factor （G-CSF） treatment,the growth of processes in cul-tured rat retinal ganglion cells （RGCs） in vitro,expression of growth associated protein 43,and expression of microtubule-associated protein 2 mRNA expression were significantly increased.In contrast,RhoA/Rock protein content was significantly reduced by G-CSF treatment.These results indicate that G-CSF promotes the growth of processes in RGCs and increases the expression of growth-associated protein 43 and microtubule-associated protein 2 mRNA by inhibiting the RhoA/Rock pathway,thereby benefiting axonal repair in RGCs exposed to hypoxia.

Mobilization Efficiency of Granulocyte Colony-stimulating Factor and Stem Cell Factor to Bone Marrow Mononuclear Cells and Mechanisms

The mobilization efficiency of granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) to bone marrow mononuclear cells (MNCs) in mice was observed, and the changes of CXCL12/CXCR4 signal were detected in order to find out the mobilization mechanism of stem cells. Kunming mice were randomly divided into two groups. The mice in treatment group were subjected to subcutaneous injection of G-CSF at a dose of 100 μg/kg and SCF at a dose of 25 μg/kg every day for 5 days, and those in control group were given isodose physiological saline. The MNCs were separated, counted and cultured, and the colony-forming unit-fibroblast (CFU-F) was evaluated. CD34+CXCR4+ MNCs were sorted by flow cytometry. The expression of CXCL12 protein in bone marrow extracellular fluid was detected by ELISA, and that of CXCL12 mRNA in bone marrow was measured by RT-PCR. The results showed that the counts of MNCs in peripheral blood and bone marrow were increased after administration of G-CSF/SCF (P<0.01). The factors had a dramatic effect on the expansion capability of CFU-F (P<0.05). Flow cytometric of bone marrow MNCs surface markers revealed that CD34+CXCR4+ cells accounted for 44.6%±8.7% of the total CD34+ MNCs. Moreover, G-CSF/SCF treatment induced a decrease in bone marrow CXCL12 mRNA that closely mirrored the fall in CXCL12 protein. In this study, it is evidenced that G-CSF/SCF can effectively induce MNCs mobilization by disrupting the balance of CXCL12/CXCR4 signaling pathway in the bone marrow and down-regulating the interaction of CXCL12/CXCR4.

Anti-apoptotic effects of recombinant human granulocyte colony-stimulating factor in focal cerebral ischemic rats

The neuroprotective effects of granulocyte colony-stimulating factor in cerebral ischemia/reperfusion injury are currently contentious. The present study examined the effects of subcutaneous injection of recombinant human granulocyte colony-stimulating factor （50 pg/kg） over 5 days in a model of cerebral ischemia/reperfusion with intraluminal filament occlusion in rats. The results indicated that recombinant human granulocyte colony-stimulating factor reduced brain infarct volume following cerebral ischemia/reperfusion injury in rats, down-regulated the expression of caspase-3 mRNA （a key protease for apoptosis in the cerebral ischemia zone）, lowered the rate of neuronal apoptosis in the cerebral ischemia zone, and notably ameliorated neurological function. These results indicate that recombinant human granulocyte colony-stimulating factor has anti-apoptotic effects on neurons following focal cerebral ischemia/reperfusion injury, and exerts neuroprotective effects.

Disseminated carcinomatosis of the bone marrow caused by granulocyte colony-stimulating factor:A case report and review of literature

BACKGROUND Disseminated carcinomatosis of the bone marrow(DCBM)is a widespread metastasis with a hematologic disorder that is mainly caused by gastric cancer.Although it commonly occurs as a manifestation of recurrence long after curative treatment,the precise mechanism of relapse from dormant status remains unclear.Granulocyte colony-stimulating factor(G-CSF)can promote cancer progression and invasion in various cancers.However,the potential of G-CSF to trigger recurrence from a cured malignancy has not been reported.CASE SUMMARY A 55-year-old Japanese woman was diagnosed with Ewing sarcoma localized on the fifth lumbar vertebrae 6 years after curative gastrectomy for T1 gastric cancer.After palliative surgery to release nerve compression,pathological diagnosis of the resected specimen was followed by curative radiation and chemotherapy.During treatment,G-CSF was administered 32 times for severe neutropenia prophylaxis.Eight months after completing definitive treatment,she complained of severe back pain and was diagnosed as multiple bone metastases with DCBM from gastric cancer.Despite palliative chemotherapy,she died of disseminated intravascular coagulation 13 d after the diagnosis.Immunohistochemical examination of the autopsied bone marrow confirmed a diffuse positive staining for the G-CSF receptor(G-CSFR)in the relapsed gastric cancer cell cytoplasm,whereas the primary lesion cancer cells showed negative staining for G-CSFR.In this case,G-CSF administration may have been the key trigger for the disseminated relapse of a dormant gastric cancer.CONCLUSIONWhen administering G-CSF to cancer survivors,recurrence of a preceding cancer should be monitored even after curative treatment.

A New Protocol for Solubilization, Refolding and Purification of Recombinant Human Granulocyte Colony-stimulating Factor in Inclusion Bodies

Recombinant human granulocyte colony-stimulating factor （rhG-CSF） in inclusion bodies was solubilized by 8 mol/L urea solution and subsequently precipitated by acetone to improve its purity. After that, the precipitates were solubilized by sodium hydroxide solution containing 2 mol/L urea. Then the solubilized rhG-CSF was passed through a size exclusion chromatography for refolding and extensive purification, and further purified by a weak anion exchange chromatography. The purity and mass recovery of refolded rhG-CSF were 96.5% and 75.6%, respectively. The bioactivity was 8.4x10^7 IU/mg.

Granulocyte Colony-Stimulating Factor Enhances the Anticancer Effects of Cisplatin against Lung Cancer by Promoting Angiogenesis

The G-CSF is used as a therapeutic drug of the febrile neutropenia in lung cancer chemotherapy, however, there were few reports that showed the effects of combination effects of G-CSF and anticancer drugs against lung cancer. In the present study, we investigated the effects of G-CSF and the combination effects of G-CSF and cisplatin on lung cancer growth. We investigated the effect of G-CSF against the LL-2 and KLN-205 cells by MTT assay and tried to detect the G-CSF receptor by RT-PCR. Next, to analyze the G-CSF effects in vivo, we transplanted the LL-2 into C57BL/6 mice, intraperitoneally administered G-CSF (30 micro/kg/day) with or without cisplatin (5 mg/kg), measured the tumor size and analyzed pathologically by HE and immunostaining. In vitro analyses, G-CSF showed no effects in LL-2 and KLN-205 cells, and RT-PCR revealed no G-CSF receptor mRNA. In vivo analyses, G-CSF alone did not significantly suppress tumor growth. However, concurrent G-CSF administration with cisplatin significantly enhanced the tumor suppressing effect of cisplatin in early stage of tumor growth. The analysis data of vWF immunostaining indicated that the neovascularization in the peripheral region of the tumors was more enhanced in G-CSF treatment mice. ELISA assay revealed that G-CSF did not influence the serum concentration of TNF-alpha and IL-12 in tumor-bearing mice. This study suggests that concurrent (combination) administration of cisplatin with G-CSF is a safe and effective method for enhancing anticancer effects and reducing chemotherapeutic agent-induced myelosuppression.

Effects of granulocyte colony-stimulating factor and stem cell factor, alone and in combination, on the biological behaviours of bone marrow mesenchymal stem cells

Aim: The effects of granulocyte colony- stimu-lating factor (G-CSF) and stem cell factor (SCF) on the proliferation and osteogenic differentia-tion capacity of bone marrow mesenchymal stem cells (MSCs) were studied in the experi-ment. Methods: Bone marrow MSCs were col-lected from rabbits successfully, and treated with various concentrations of G-CSF, SCF or a combination of the two. Flow cytometric ana-lyse, MTT test, CFU-F assay, and alkaline phosphatase (ALP) activity measurement were employed. Results: The results of flow cytome-try showed that immunophenotype of the cells were CD29+/CD45-, CD105+/ CD34–, CD90+/ HLADR–. MSCs were shown to constitutively express low levels of c-kit which could be en-hanced by SCF. G-CSF and SCF had an obvious facilitative effect on the proliferation of MSCs in a dose-dependent fashion. In addition, G-CSF and SCF would be effective in reversibly pre-venting their differentiation, as showed by the decrease of ALP activity, leading to self-renewal rather than differentiative cell divisions. The effects of G-CSF were superior to SCF. And cells in the group treated with combination of G-CSF and SCF showed more powerful effects than the groups treated with G-CS, SCF, or none of the two. Conclusion: On the whole, these studies demonstrated that MSCs responsed to G-CSF, SCF, and to G-CSF plus SCF in a manner that suppressed differentiation, and promotes proliferation and self-renewal, and support the view that these factors could act synergistically.

Effect of granulocyte colony-stimulating factor on the cardiac function and endothelial function in patients with myocardial infarction after PCI

Objective:To explore the effect of granulocyte colony-stimulating factor (G-CSF) on the cardiac function and endothelial function in patients with myocardial infarction after percutaneous coronary intervention (PCI).Methods: A total of 76 patients with acute myocardial infarction treated in our hospital between August 2012 and January 2016 were collected and divided into observation group and control group (n=38) according to the randomized parallel control method. Control group of patients received PCI treatment, and observation group of patients received G-CSF treatment (5 μg/kg, subcutaneous injection, 3 times/d, for 5 d) after PCI. 2 weeks after treatment, color Doppler diasonograph was used to detect cardiac function parameters, RIA method was used to detect serum cardiac function indexes, and enzyme-linked immunosorbent assay (ELISA) was used to detect serum endothelial function indexes.Results:Before treatment, differences in serum cardiac function index and endothelial function index levels were not statistically significant between two groups of patients. 2 weeks after treatment, cardiac output (CO) and stroke volume (SV) levels of observation group were significantly higher than those of control group while left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) levels were lower than those of control group;serum heart-type fatty acid-binding protein (H-FABP), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and Galectin-3 levels of observation group were lower than those of control group, endothelin-1 (ET-1) level was lower than that of control group, and nitric oxide (NO) level was higher than that of control group.Conclusion:G-CSF can enhance the cardiac function after PCI and also optimize the endothelial function in patients with myocardial infarction.

Granulocyte colony-stimulating factor reduces biliary fibrosis and ductular reaction in a mouse model of chronic cholestasis

Background:Biliary atresia is a rare congenital bile duct disease that is the leading cause of liver fibrosis in neonates.Granulocyte colony-stimulating factor(GCSF)is a potential therapy for hepatocellular diseases,but data on GCSF for cholestatic conditions remain limited.Materials and methods:The current study examines the role of GCSF in improving bile duct obstruction in mice.Two doses were administered:10.0 mg/kg/day and 61.5 mg/kg/day,which is the animal equivalent dose of 5.0 mg/kg in humans.Seven days(D7)after bile duct ligation(BDL),Swiss mice were treated with phosphate buffered saline or GCSF for 5 days.The intrahepatic adaptive response of BDL mice was evaluated on postsurgical days D12,D19,and D26.Results:Treatment with 61.5 mg/kg of GCSF resulted in a significant increase in circulating leukocytes and neutrophils on D12.Amelioration of liver injury,as shown by reduced aspartate aminotransferase levels,increased albumin levels and survival rate,as well as reduced intrahepatic inflammation and hepatic myeloperoxidase expression,downregulated ductular proliferation,periportal fibroblast activation,and fibrosis,enhanced expressions of hepatocyte growth factor,peroxisome proliferator-activated receptoralpha,and ki67,and suppressed expression of cleaved caspase-3 protein,was noted after treatment with 61.5 mg/kg of GCSF.Additionally,GCSF treatment was associated with an increased number of intrahepatic cd3-Sca1tc-Kitt bone marrow cells.

A retrospective study of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing neutropenia during definitive concurrent chemoradiotherapy in patients with esophageal squamous carcinoma

Objective:To compare the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF)for preventive or delayed treatment in neutropenia,completion rate of concurrent chemoradiotherapy and hospitalization rate in patients with esophageal squamous carcinoma during definitive concurrent chemoradiotherapy.Methods:A total of 70 patients with esophageal squamous carcinoma in Peking University Cancer Hospital from January 2019 to December 2020,who received PEG-rhG-CSF during concurrent chemoradiotherapy,were enrolled in this retrospective analysis.There were 32 patients in the preventive group,and 38 patients in the delayed group.The incidence of neutropenia,completion rate of concurrent chemoradiotherapy and neutropeniarelated hospitalization rate were compared between PEG-rhG-CSF preventive group and delayed group.Results:The incidence of severe neutropenia(Grades 3–4)in all patients was 31.4%.Comparison between preventive group and delayed group showed that the incidence of severe neutropenia was 6.3%and 39.4%(χ^(2)=10.428,P=0.001),respectively.In preventive group,the incidence of severe neutropenia was 3.7%and 20.0%,respectively,for primary prevention and secondary prevention of PEG-rhG-CSF(χ^(2)=12.321,P=0.001).The completion rate of concurrent chemoradiotherapy was 93.8%in the preventive group and 63.2%in the delayed group(χ^(2)=9.220,P=0.002).The incidence of treatment interruption was 25.7%in the whole group,12.5%in the preventive group and 36.8%in the delayed group(χ^(2)=5.389,P=0.020).Seven patients(7/70,10.0%)were hospitalized and treated with intravenous antibiotics for neutropenia,including 1 in the preventive group and 6 in the delayed group(P=0.078).Conclusions:Prophylactic use of PEG-rhG-CSF during concurrent chemoradiotherapy for patients with esophageal squamous carcinoma can effectively reduce the incidence of neutropenia,ensure the safety of treatment,and improve the completion rate of concurrent chemoradiotherapy.

Combined treatment with erythropoietin and granulocyte colony-stimulating factor enhances neovascularization and improves cardiac function after myocardial infarction

Background Erythropoietin （EPO） and granulocyte colony-stimulating factor （G-CSF） are both potential novel therapeutics for use after myocardial infarction （MI）.However,their underlying mechanisms remain unclear and the efficacy of monotherapy with EPO or G-CSF is also controversial.Therefore,we investigated the effects of combined treatment with EPO and G-CSF on neovascularization and cardiac function in post-infarction rats and explored the potential mechanisms.Methods Four groups of rats were used：control （saline injection after MI,i.h.）,EPO （a single dose of 5 000 IU/kg after MI,i.h.）,G-CSF （a dose of 50 μg· kg-1· d-1 for 5 days after MI,i.h.）,and both EPO and G-CSF （EPO＋G-CSF,using the same regiment as above）.Cardiac function was assessed by echocardiography before and 1 day,7 days,14 days and 21 days after MI.CD34＋/Flk-1＋ cells in the peripheral blood were evaluated by flow cytometry before and 3 days,5 days and 7 days after MI.The infarct area and angiogenesis in the peri-infarct area were analyzed.The mRNA and protein expression of vascular endothelial growth factor （VEGF） and stromal-derived factor-1α （SDF-1α） in the peri-infarct area were detected by real-time quantitative RT-PCR and Western blotting.Results Compared with the control and monotherapy groups,the EPO＋G-CSF group had significantly increased CD34＋/ Flk-1＋ endothelial progenitor calls （EPCs）in the peripheral blood （P ＜0.05）,up-regulated VEGF and SDF-1α levels in the peri-infarct region （P ＜0.05）,enhanced capillary density （P ＜0.05）,reduced infarct size （P ＜0.05） and improved cardiac structure and function （P ＜0.05）.G-CSF alone did not dramatically increase EPCs in the peripheral blood,enhance capillary density in the peri-infarct area or reduce infarct size compared with the control group.Conclusions Combined treatment with EPO and G-CSF increased EPCs mobilization,up-regulated VEGF and SDF-1α levels in the post-infarction microenvironment,subsequently enhanced neovascularization in the peri-infarct region and reduced infarct size.All factors contributed to its beneficial effects on cardiac function in post-infarction rats.

Influence of granulocyte colony-stimulating factor on cardiac function in patients with acute myocardial infarction and leukopenia after revascularization

Background Granulocyte colony-stimulating factor （G-CSF） seems to improve cardiac function and perfusion when used systemically through mobilization of stem cells into peripheral blood, but results of previous clinical trials remain controversial. This study was designed to investigate safety and efficacy of subcutaneous injection of G-CSF on left ventricular function in patients with impaired left ventricular function after ST-segment elevation myocardial infarction （STEMI）. Methods Thirty-three patients （22 men; age, （68.5±6.1） years） with STEMI and with comorbidity of leukopenia were included after successful primary percutaneous coronary intervention within 12 hours after symptom onset. Patients were randomized into G-CSF group who received G-CSF （10 μg/kg of body weight, daily） for continuous 7 days and control group. Results of blood analyses, echocardiography and angiography were documented as well as possibly occurred adverse events. Results No severe adverse events occurred in both groups. Mean segmental wall thickening in infract segments increased significantly at 6-month follow up compared with baseline in both groups, but the longitudinal variation between two groups had no significant difference （P〉0.05）. The same change could also be found in longitudinal variation of wall motion score index of infarct segments （P 〉0.05）. At 6-month follow-up, left ventricular end-diastolic volume of both groups increased to a greater extent, but there were no significant differences between the two groups when comparing the longitudinal variations （P 〉0.05）. In both groups, left ventricular ejection fraction measured by echocardiography ameliorated significantly at 6-month follow-up （P 〈0.05）, but difference of the longitudinal variation between two groups was not significant （P 〉0.05）. When pay attention to left ventricular ejection fraction measured by angiocardiography, difference of the longitudinal variation between groups was significant （P=0.046）. Early diastolic mitral flow velocity deceleration time changed significantly at 6- month follow-up in both groups （P=-0.05）. Conclusions Mobilization of stem cells by G-CSF after reperfusion of infarct myocardium is safe and seems to offer a pragmatic strategy for recovery of myocardial global function.

Granulocyte colony-stimulating factor ameliorates coronary artery elastin breakdown in a mouse model of Kawasaki disease

Background Coronary artery damage from Kawasaki disease （KD） is closely linked to the dysfunction of the endothelial progenitor cells （EPCs）.The aim of the present study was to evaluate the modulatory effect of granulocyte colony stimulating factor （G-CSF） on EPCs and elastin breakdown of coronary arteries in a KD mouse model.Methods A Lactobacillus casei cell wall extract （LCWE）-induced KD model was established in C57BL/6 mice that were subsequently administrated with recombinant human G-CSF （rhG-CSF）.Nω-nitro-L-arginine methyl ester （L-NAME） was administrated for the negative intervention.Evaluations included coronary artery lesions,EPC number and functions,and the plasma concentration of nitric oxide （NO）.Results Elastin breakdown was found in the coronary arteries of model mice 56 days after injection of LCWE.The number of circulating EPCs,plasma concentration of NO,and functions of bone marrow EPCs,including proliferation,adhesion,and migration abilities,were all lower in the KD model group compared with those in the control group.After administration of rhG-CSF,the number of circulating EPCs and plasma concentration of NO were increased significantly compared with those in the KD model group.There were also increases in the functional indexes of EPCs.Furthermore,rhG-CSF administration improved the elastin breakdown effectively.However,these protective effects of rhG-CSF on coronary arteries were attenuated by L-NAME.Conclusion The present study indicated that the administration of G-CSF prevents elastin breakdown of the coronary arteries by enhancing the number and functions of EPCs via the NO system,and then accelerates the repair of coronary artery lesions in the KD.