Currently, platelet transfusion is the primary treatment for thrombocytopnia which results from intensive chemotherapy and radiotherapy of cancer. While repeated platelet transfusions are associated with several problems. The clinical availability of safe and effective platelet growth factors is eagerly awaited. Currently, a mumber of hematopoietic growth factors with thrombopoietic activity have been identified. This review discusses the biological characteristics and the clinical trial investigation development of platelet growth factors.

Objective:To investigate the relationship of-308bp polymorphism in tumor necrosis factor-α (TNFa)gene and+252bp in lymphotoxin-α(LTα)gene with the clinical course and outcome of non-Hodgkin's lymphoma(NHL).Methods:The single base change in TNFα gene and LTα gene was analyzed among 96 Chinese patients with NHL and 72 normal controls by using PCR-restrictive fragment length polymorphism (RFLP).The clinical data were collected and survival analysis was performed.Results:In NHL patients,no statistcally significant association was found between the presence of a given TNF/LT haplotype status and clinical variables such as age,seX,disease stage,and so on.The patients carrying low-risk haplotype achieved a more sensitive response to first-line therapy than that in patients with high-risk haplotype(70.4%v 45.2%:P=0.018).The estimated 1-year progression-free survival rates in the high-risk and low-risk groups were 66.67% and 87.5%,respectively(log-rank test,P=0.0231).Kaplan-Meier method showed that the estimated 2-year and 4-year overall survival rates were 39.95%and 8.32%in patents carrying high-risk haplotypes and 65.13%and 46.52%in patients carrying low-risk haplotypes,respectively(log-rank test,P=0.0012).In multivariate Cox regression models.the TNF/LT haplotype status was found to be a dsk factor for outcome of NHL (P=0.034).Conclusion:There is an association between TNF/LT haplotype status and response to therapy and outcomes of NHL in Canton area,China.Detecting TNF/LT haplotype may be a sensitive method to evaluate the outcome of NHL.

Traditional concept has been that hematopoietic stem cells (HSC) are tissue-specific stem cells, which are restricted to generate the cell types of the blood and immune system. However, recent studies have shown that there is a higher plasticity of the HSC than previous expected, it can be induced to transdifferentiated into mature cells of other nonhematopoietic organs after transplantation in vivo. In this article, the recent advances in the plasticity of HSC and its potential clinical application are reviewed.

Myelodysplastic syndromes(MDS) is a malignant disease of hematopoietic stem cell / progenitor cell clones. Therapies of MDS including immuno-suppressive drugs, chemotherapy, hemopoietic stem cell transplantation and drugs suppressing malignant clones have improved much in recent years. This review is about intervention therapy of MDS and the therapy effect.

AIM:To study the thershold of hepatocellular carcinoma (HCC) apoptosis induced by adriamycin (ADM) and cis-diamminedichloroplatinum(CDDP). METHODS: Using primary human hepatocellular carcinoma culture, immunofluorescence staining of Hoechst 33 258 in HCC cells ,and flow cytometric assay. RESULTS:24 h after HCC cells were cultured with ADM or CDDP, it were found there were dispersive fluorescences in normal cells nuclei, and compact particulate fluorescences in apoptosis cells nuclei by immunofluorescence staiming of Hoechst 33 258. The rate of HCC cells apoptosis was dependent on doses of ADM and CDDP. HCC cells apoptotic threshold were determined, i.e.ADM was 1.0 ?g/mL and CDDP was 1.5?g/mL (The clinical apoptotic sensitive dosages were ADM 20 mg/m2 and CDDP 30 mg/m2. CONCLUSION: HCC cells apototic threshold of ADM and CDDP were efficient in clinical chemotherapy.

As a major component of the hematopoietic microenvironment,stromal cells have been proved to support hematopoiesis. This review describes the constitution, origin of stromal cells and its mrechanism of regulate hematopoiesis, and then elaborates that the stromal cells play a important role in the hematopoietic restitution of hematopoietic stem cell transplantation.

AIM:To investigate effect of recombinant human thrombopoietin on exsanguine thrombocytopenia mice. METHODS:Normal peripheral platelet counts were performed on sample obtained from the tail vein of purebred Babl/c mice including experimental and control groups before experimentation. rhTPO was injected into the mice by intraperitoneal injection once a day for 7 days. On the seventh and the fourteenth day, the mice were phlebotomized from the supra-obitalis vein in order to make exsanguine thrombocytopenia animal model. At the same time, we observed the biological activity of recombinant human thrombopoietin in vivo and the mice's death rate. RESULTS: On the seventh day and the fourteenth day, platelet counts of mice treated by rhTPO were higher than those by PBS (P＜0.05). Moreover the platelet counts of mice in experimental group of rhTPO showed increasing tendency following experimental days. In addition, death happened in two groups after those mice were phlebotomized from the supra-obitalis vein, but the death rate in negative control group was evidently higher than that in experimental group (P＜0.05). CONCLUSION:rhTPO had obvious biological activity in increasing platelet production, which resulted in the drop in thrombocytopenia mice's death rate.

BACKGROUND:Granulocyte colony-stimulating factor (G-CSF) can strongly mobilize bone marrow hematopoietic stem cells (HSCs). It has been proved that G-CSF has the ability to mobilize both HSCs and mesenchymal stem cells (MSCs).OBJECTIVE:To investigate the therapeutic effect of G-CSF in mobilizing autologous bone marrow stem cells entering cerebral infarction zone on ischemic cerebral infarction in rats.DESIGN:A randomized grouping design, animal experiment.SETYING: Center for Stem Cell Biology and Tissue Engineering of Sun Yat-sen University.MATERIALS: This experiment was carried out at the Animal Experimental Department of Sun Yat-sen University (North District) and Center for Stem Cell Biology and Tissue Engineering of Sun Yat-sen University from September 2004 to January 2005. Totally 200 male Wistar rats were chosen and randomly divided into autologous bone marrow stem cells transplantation group and control group, with 100 rats in each group.METHODS:Rats of two groups were made cerebral infarction models by line occlusion. Transplantation group introduced intraperitoneal injection of 60 μg/kg G-CSF one hour after operation. The control group introduced intraperitoneal injection of saline of the same dosage at the same time. ①All rats were weighed before operation and 24 hours, 48 hours, one week after operation to evaluate body mass loss rate. They were also given neurological grading. Grading criteria: Grade 0 is normal. Grade Ⅰ is that the right forelimb bends. Grade Ⅱ is that the right forelimb grasped weakly when the tail is lifted. Grade Ⅲ is that the rat has no directivity in automatic action and circumrotates to right when the tail is lifted. Grade Ⅳ is that the rat circumrotates to right in automatic action. ②15 rats in each group were selected. 24 hours, 48 hours, one week after operation, we opened the skulls, took out the brain and used 2,3,5-Triphenyltetrazoluim Chloride (TTC) staining to measure infarction volume, hematoxylin-eosin(HE) staining to observe the pathological change , and immunohistochemistry to detect the infiltration of CD34+ cells.MAIN OUTCOME MEASURES:Body mass loss rate, neurological grade,infarction volume, pathological change and infiltration of CD34+ cells.RESULTS: Totally 180 of 200 rats were successfully made cerebral infarction model. 48 rats died in seven days after operation. As a result, 132 rat models were alive and 120 rats were randomly selected for data analysis. ①Measurement of body mass and neurological grading: There was no significant difference in body mass loss rate between two groups 24 hours and 48 hours after operation (P ＜ 0.05);one week after operation, body mass loss rate was significantly lower in transplantation group [(10.5±8.2)%]than in control group [(17.8±7.1)%] (P ＜ 0.05). There was no significant difference in neurology grade between two groups. ②Infarction volume:Infarction volume and the percent of infarction volume in the whole brain in control group were all higher than those in the transplantation group,with significant difference [ (251.69±52.77) mm3 vs(145.72±28.05)mm3,(17.00±2.69)% vs (9.90±1.62)% ,P ＜ 0.01]. ③Pathological change: 24 hours after operation, the brain tissue of two groups got classical pathological change of cerebral ischemia infarction. There were some mono-nucleus cells infiltrating in transplantation group while none in control group. 48 hours after operation, most nerve cells disappeared and the glial cells were degenerated. There were many mono-nucleus cells infiltrating in transplantation group while a few in control group. One week after operation, tissues in the infarction zone were liquescent with many monocaryons and lymphocytes infiltrating around them in control group. In transplantation group, part of the infarction zone was plerosised through proliferation of newly born capillaries and glial cells and inflammatory cells were not evident. ④Immunohistochemistry: CD34+ mono-nucleus cells were detected in the ischemic territory in transplantation group 24 hours after operation while none in the brain of other side and control group. There were CD34+ mono-nucleus cells and pyramidate cells with mutations in transplantation group 48 hours after operation while none in the brain of other side and control group.CONCLUSION:The stem cell transplantation in situ therapy, which employs self-marrow stem cells mobilized by G-CSF can relieve the ischemic degree and reduce the infarction volume.

BACKGROUND: Differentiation of bone marrow mesenchymal stem calls(BMSCs) is associated with their microenvironment. After acute myocardial infarction (AMI), the necrosis of cardiomyocytes caused activation of complement, generation of free radical, and secretion of various cell factors. As a result, the ingredients of patients' serum also changed, so does the changes will influence the differentiation of BMSCs into cardiomyocytes? And what influence it will be? OBJECTIVE: To investigative effects of AMI rat serum on the differentiation of BMSCs into cardiomyocytes. DESIGN, TIME AND SETTING: The in vitro controlled cytology experiment was performed at the Laboratory of Center for Stem cells and Tissue Engineering, Sun Yat-sen University from September in 2005 to June in 2006. MATERIALS: SPF Sprague Dawley rats, weighing 50-80 g, aged 3-4 weeks, were used for culture of BMSCs, and SpragueDawley rats, weighing 200-300 g, aged 6-8 weeks, were used for making AMI models. METHODS: BMSCs were isolated and cultured with the adherent method. After making AMI rat models by deligating anterior descending of the left coronary artery, the serum were collected and centrifuged from AMI and normal rats. Then the passage 3 of BMSCs were divided into six groups, non-induction group, 5-azacytidine (5-aza) group, 5-aza plus serum from AMI rat group, 5-aza plus serum from normal rat group, serum from AMI rat group, and serum from normal rat group. MAIN OUTCOME MEASURES: Morphology changes in rat BMSCs after induction; Expression of cardiac troponin T of BMSCs after induction; Expression of GATA-4 and desmin mRNA of BMSCs after induction. RESULTS: After being induced by 5-aza and two kinds of serum, some cells became elongated and thinner. Two to three weeks after induction, some cells had a ball-like or rod-like appearance, and connection were formed between adjacent cells. It showed that some BMSC have differentiated into cardiac like cells. The expression of cardiac troponin T, GATA-4 and desmin were positive in cells differentiated from BMSCs. The troponin T expression in control group and simple serum induction group were negative, but GATA-4 and desmin expressed weakly. CONCLUSION: Serum from AMI rat cannot induce BMSCs to differentiate into cardiomyocytes alone, but it promotes BMSCs induced by 5-aza differentiating into cardiomyocytes and facilitates the differentiated calls into mature.

Objective To investigate the influence of the PBSC collection yield by choosing the differ-era venous accesses in the healthy donors. Methods 118 healthy PBSC donors performing PBSC collection between January 2000 and December 2007 in our hospital were divided into four groups according to the differ-ent venous accesses. The PBSC collection yield of four groups,including mononuclear cells (MNC) count and CD34+ cells count were observed. Results In the ulnar V-ulnar V group,MNC (5.31±2.29)×108/kg,CD34+ cells (4.78±2.06)×106/kg;ulnar V- antecubital V group,MNC(5.11±2.34)×108/kg,CD34+cells(4.34±1.99)×106/kg;antecubital V- antecubital V group,MNC (5.61±1.73)±×108/kg,CD34+cells (4.60±1.42)×106/kg;ulnar V- radial V group,MNC(4.60±×1.70)×108/kg,CD34+cells (4.05±1.50)×106/kg.There was no statistical differ-ence of the PBSC collection yield between four groups (P>0.05). Conclusions Different venous accesses don't affect the PBSC collection yield in the PBSC healthy donors.