Propofol injection combined with bone marrow mesenchymal stem cell transplantation better improves electrophysiological function in the hindlimb of rats with spinal cord injury than monotherapy

The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to explore the therapeutic effects of their combination on spinal cord injury. Rat models of spinal cord injury were established using the weight drop method. Rats were subjected to bone marrow mesenchymal stem cell transplantationvia tail vein injection and/or propofol injectionvia tail vein using an infusion pump. Four weeks after cell transplan-tation and/or propofol treatment, the cavity within the spinal cord was reduced. The numbers of PKH-26-positive cells and horseradish peroxidase-positive nerve ifbers apparently increased in the spinal cord. Latencies of somatosensory evoked potentials and motor evoked potentials in the hindlimb were noticeably shortened, amplitude was increased and hindlimb motor function was obviously improved. Moreover, the combined effects were better than cell transplantation or propofol injection alone. The above data suggest that the combination of propofol injection and bone marrow mesenchymal stem cell transplantation can effectively improve hindlimb electro-physiological function, promote the recovery of motor funtion, and play a neuroprotective role in spinal cord injury in rats.

Effects of blood transfusion on bone marrow transplantation for the survival of rats after total lymphoid irradiation treated with cyclophosphamide

Rats,after inflicted with total lymphoid irradiation (TLI) of 10 Gy gamma rays (lethal dose) and treated with cyclophosphamide (CY),were further treated with bone marrow transplantation (BMT). Then the effects of blood transfusion (BT) on the therapeutic effects of BMT and the survival of the rats were observed. It was found that after TLI and CY treatment, the rats were further treated with BT and all the animals died in 4-12 d after TLI. The 60 day survival rate of the rats treated 1 d after BMT with BT from the same donor of bone marrow and that of those rats treated with BMT only was 10% and that of those rats treated 1 d before BMT with BT from the same donor of bone marrow or from another donor was 20% and 40% respectively (P<0. 05). And the rats treated 3 d before BMTwith BT from the same donor of bone marrow all died of allergic reaction in 4-10 d after TLI. When CY was administered in divided doses, the 60-day survival rate of the rats treated 1 d before BMT with BT from the same donor of bone marrow was increased to 80%(PM0. 01). These findings indicate that the effects of BT on the enhancement of the therapeutic effects of BMT on radiation injury is determined with the time of BT.

Improvement of neurological function in rats with spinal cord injury after the transplantation of neural stem cells directly differentiated from bone marrow mesenchymal stem cells

Objective To study the effect and mechanism of neurological function recovery in rats with spinal cord injury ( SCI) rats after transplantation of neural stem cells which are directly differentiated from bone marrow mesenchymal stem cells ( BMSC ) ,and to investigate the suitable engraftment time. Methods BMSC at 3rd passage were differentiated into neural stem cells ( NSC) , and immunofluorescence staining was used to

Phase 1 human trial of autologous bone marrow-hematopoietic stem cell transplantation in patients with decompensated cirrhosis

AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients.RESULTS: Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Because of the major side effects seen in the last patient, the trial was prematurely stopped.CONCLUSION: Infusion of CD34+ stem cells through the hepatic artery is not safe in decompensated cirrhosis. Radiocontrast nephropathy and hepatorenal syndrome could be major side effects. However, this study doesnot preclude infusion of CD34+ stem cells through other routes.

Transplantation of bone marrow-derived endothelial progenitor cells and hepatocyte stem cells from liver fibrosis rats ameliorates liver fibrosis

AIM To explore the effectiveness for treating liver fibrosisby combined transplantation of bone marrow-derived endothelial progenitor cells(BM-EPCs) and bone marrow-derived hepatocyte stem cells(BDHSCs) from the liver fibrosis environment.METHODS The liver fibrosis rat models were induced with carbon tetrachloride injections for 6 wk. BM-EPCs from rats with liver fibrosis were obtained by different rates of adherence and culture induction. BDHSCs from rats with liver fibrosis were isolated by magnetic bead cell sorting. Tracing analysis was conducted by labeling EPCs with PKH26 in vitro to show EPC location in the liver. Finally, BM-EPCs and/or BDHSCs transplantation into rats with liver fibrosis were performed to evaluate the effectiveness of BM-EPCs and/or BDHSCs on liver fibrosis.RESULTS Normal functional BM-EPCs from liver fibrosis rats were successfully obtained. The co-expression level of CD133 and VEGFR2 was 63.9% ± 2.15%. Transplanted BM-EPCs were located primarily in/near hepatic sinusoids. The combined transplantation of BM-EPCs and BDHSCs promoted hepatic neovascularization, liver regeneration and liver function, and decreased collagen formation and liver fibrosis degree. The VEGF levels were increased in the BM-EPCs(707.10 ± 54.32) and BM-EPCs/BDHSCs group(615.42 ± 42.96), compared with those in the model group and BDHSCs group(P < 0.05). Combination of BM-EPCs/BDHSCs transplantation induced maximal up-regulation of PCNA protein and HGF m RNA levels. The levels of alanine aminotransferase(AST), aspartate aminotransferase, total bilirubin(TBIL), prothrombin time(PT) and activated partial thromboplastin time in the BMEPCs/BDHSCs group were significantly improved, to be equivalent to normal levels(P > 0.05) compared with those in the BDHSC(AST, TBIL and PT, P < 0.05) and BM-EPCs(TBIL and PT, P < 0.05) groups. Transplantation of BM-EPCs/BDHSCs combination significantly reduced the degree of liver fibrosis(staging score of 1.75 ± 0.25 vs BDHSCs 2.88 ± 0.23 or BMEPCs 2.75 ± 0.16, P < 0.05).CONCLUSION The combined transplantation exhibited maximal therapeutic effect compared to that of transplantation of BM-EPCs or BDHSCs alone. Combined transplantation of autogenous BM-EPCs and BDHSCs may represent a promising strategy for the treatment of liver fibrosis, which would eventually prevent cirrhosis and liver cancer.

Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease

AIM： To evaluate the safety and feasibility of bone marrow cell （BMC） transplantation in patients with chronic liver disease on the waiting list for liver transplantation. METHODS： Ten patients （eight males） with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells. Seven patients were classified as Child-Pugh B and three as Child-Pugh C. Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI. Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient. At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors. Patients were followed up for adverse events up to 4 mo. RESULTS： The median age of the patients was 52 years （range 24-70 years）. All patients were discharged 48 h after BMC infusion. Two patients complained ofmild pain at the bone marrow needle puncture site. No other complications or specific side effects related to the procedure were observed. Bilirubin levels were lower at 1 （2.19 ± 0.9） and 4 mo （2.10 ± 1.0） after cell transplantation that baseline levels （238 ± 1.2）. Albumin levels 4 mo after BMC infusion （3.73 ± 0.5） were higher than baseline levels （3.47 ± 0.5）. International normalized ratio （INR） decreased from 1.48 （SD = 0.23） to 1.43 （SD = 0.23） one month after cell transplantation. CONCLUSION： BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed. Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease.

Electrophysiological functional recovery in a rat model of spinal cord hemisection injury following bone marrow-derived mesenchymal stem cell transplantation under hypothermia

Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein while maintaining rectal temperature at 34 ± 0.5°C for 6 hours （mild hypothermia）. Hematoxylin-eosin staining showed that astrocytes gathered around the injury site and formed scars at 4 weeks post-transplantation. Compared with rats transplanted with bone marrow stem cells under normal temperature, rats transplanted with bone marrow stem cells under hypothermia showed increased numbers of proliferating cells （bromodeoxyuridine-positive cells）, better recovery of somatosensory-evoked and motor-evoked potentials, greater Basso, Beattie, and Bresnahan locomotor rating scores, and an increased degree of angle in the incline plate test. These findings suggested that hypothermia combined with bone marrow mesenchymal stem cells transplantation effectively promoted electrical conduction and nerve functional repair in a rat model of spinal cord hemisection injury.

Effects of Guiyuanfang and autologous transplantation of bone marrow stem cells on rats with liver fibrosis

AIM: To investigate the therapeutic effects of Guiyuanfang and bone marrow stem cells (BMSCs) on rats with liver fibrosis.METHODS: Liver fibrosis model was induced by carbon tetrachloride, ethanol, high lipid and assessed biochemically and histologically. Liver function and hydroxyproline contents of liver tissue were determined.Serum hyaluronic acid (HA) level and procollagen Ⅲ level were performed by radioimmunoassay. The VG staining was used to evaluate the collagen deposit in the liver.Immunohistochemical SABC methods were used to detect transplanted BMSCs and expression of urokinase plasminogen activator (uPA).RESULTS: Serum transaminase level and liver fibrosis in rats were markedly reduced by Guiyuanfang and BMSCs. HA level and procollagen Ⅲ level were also reduced obviously,compared to model rats (HA: 47.18±10.97 ng/mL,48.96±14.79 ng/mL; PCⅢ: 22.48±5.46 ng/mL, 26.90±3.35ng/mL; P＜0.05).Hydroxyproline contents of liver tissue in both BMSCs group and Guiyuanfang group were far lower than that of model group (1 227.2±43.1 μg/g liver tissue, 1390.8±156.3 μg/g liver tissue; P＜0.01). After treatment fibrosis scores were also reduced. Both Guiyuanfang and BMSCs could increase the expression of uPA. The transplanted BMSCs could engraft, survive, and proliferate in the liver.CONCLUSION: Guiyuanfang protects against liver fibrosis.Transplanted BMSCs may engraft, survive, and proliferate in the fibrosis livers indefinitely. Guiyuanfang may synergize with BMSCs to improve recovery from liver fibrosis.

The future of bone marrow stromal cell transplantation for the treatment of spinal cord injury

Bone marrow stromal cell （BMSC） transplantation therapy is a promising approach for treating spinal cord injury （SCI）, based on a number of experimental and clinical reports （Wright et al., 2011）. BMSCs are a source of neuroregenerative somatic stem cells that are without the potential for tumorigenicity. Although clinical studies of autologous BMSC transplantation have been reported in Asia （fiang et al., 2013; Yoon et al., 2007）, in Japan, it is currently an uncommon procedure and highly controversial as well. This perspective paper provides an overview of the clinical effectiveness of BMSC trans- 191antation and a proposal to enhance its use as a viable therapy.

Overexpression of vascular endothelial growth factor enhances the neuroprotective effects of bone marrow mesenchymal stem cell transplantation in ischemic stroke

Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor(VEGF)on behavioral defects in a rat model of transient cerebral ischemia,which was induced by middle cerebral artery occlusion.VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke.We found that compared with the stroke-only group and the vehicle-and BMSCs-control groups,the VEGF-BMSCs treated animals displayed the largest benefits,as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke.Additionally,VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier,increased the regeneration of blood vessels in the region of ischemic penumbra,and reducedneuronal degeneration surrounding the infarct core.Further mechanistic studies showed that among all transplant groups,VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor.These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.

Influence of Transplantation of Allogenic Bone Marrow Mononuclear Cells on the Left Ventricular Remodeling of Rat after Acute Myocardial Infarction

To probe into the influence of transplantation of allogenic bone marrow mononuclear cells （BM-MNCs） on the left ventricular remodeling of rat after acute myocardial infarction （AMI）, 60 male Wistar rats were evenly divided into three groups at random： control group 1, control group 2 and transplantation group. In control group 1, chest was opened without ligation of coronary artery; in control group 2 and transplantation group, the left anterior descending branch of coronary artery was ligated to establish AMI model. Prepared culture medium and allogenic BM-MNCs suspension were respectively implanted the surrounding area of infracted cardiac muscle via epicardium of control group 2 and transplantation group. Four weeks after the operation, the osteopontin gene （OPN mRNA, P〈0.01）, type Ⅰ collagen （P〈0.01） and angiotensin Ⅱ （AngⅡ, P〈0.01） content in the left ventricular non-infracted myocardium, and the Ang Ⅱ density in blood plasma （P〈0.05） of transplantation group and control group 2 were all significantly higher than that of control group Ⅰ. In the transplantation group, the myocardial OPN InRNA, type Ⅰ collagen and Ang Ⅱ content of non-infracted zone in left ventricle, and the Ang Ⅱ concentration in blood plasma were all significantly lower than those of control group 2 （P〈0.05 for all）. It is concluded that allogenic BM-MNCs transplantation may ease left ventricular remodeling after AMI by inhibiting the synthesis of type Ⅰ collagen in the cardiac muscle and down-regulating the expression of Ang Ⅱ and OPN gene.

Improvement of learning and memory abilities and motor function in rats with cerebral infarction by intracerebral transplantation of neuron-like cells derived from bone marrow stromal cells

BACKGROUND： Transplantation of fetal cell suspension or blocks of fetal tissue can ameliorate the nerve function after the injury or disease in the central nervous system, and it has been used to treat neurodegenerative disorders induced by Parkinson disease. OBJECTIVE： To observe the effects of the transplantation of neuron-like cells derived from bone marrow stromal cells （rMSCs） into the brain in restoring the dysfunctions of muscle strength and balance as well as learning and memory in rat models of cerebral infarction. DESIGN ： A randomized controlled experiment.SETTING ： Department of Pathophysiology, Zhongshan Medical College of Sun Yat-sen University.MATERIALS ： Twenty-four male SD rats （3-4 weeks of age, weighing 200-220 g） were used in this study （Certification number：2001A027）. METHODS： The experiments were carried out in Zhongshan Medical College of Sun Yat-sen University between December 2003 and December 2004. ① Twenty-four male SD rats randomized into three groups with 8 rats in each： experimental group, control group and sham-operated group. Rats in the experiment al group and control group were induced into models of middle cerebral artery occlusion （MCAO）. After in vitro cultured, purified and identified with digestion, the Fischer344 rMSCs were induced to differentiate by tanshinone IIA, which was locally injected into the striate cortex （18 area） of rats in the experimental group, and the rats in the control group were injected by L-DMEM basic culture media （without serum） of the same volume to the corresponding brain area. In the sham-operated group, only muscle and vessel of neck were separated. ② At 2 and 8 weeks after the transplantation, the rats were given the screen test, prehensile-traction test, balance beam test and Morris water-maze test. ③ The survival and distribution of the induced cells in corresponding brain area were observed with Nissl stained with toluidine blue and hematoxylin and eosin （HE） staining in the groups.MAIN OUTCOME MEASURES ： ① Results of the behavioral tests （time of the Morris water-maze test screen test, prehensile-traction test, balance beam test）; ② Survival and distribution of the induced cells.RESULTS： All the 24 rats were involved in the analysis of results. ① Two weeks after transplantation, rats with neuron-like cells grafts in the experimental group had significant improvement on their general muscle strength than those in the control group [screen test： （9.4±1.7）, （4.7±1.0） s, P 〈 0.01]; forelimb muscle strength [prehensile-traction test： （7.6±1.4）, （5.2±1.2） s, P 〈 0.01], ability to keep balance [balance beam test： （7.9±0.74）, （6.1±0.91） s, P 〈 0.01] and abilities of learning and memory [latency to find the platform： （35.8±5.9）, （117.5±11.6） s, P 〈 0.01; distance： （623.1±43.4）, （1 902.3±98.6） cm, P 〈 0.01] as compared with those in the control group. The functional performances in the experimental group at 8 weeks were better than those at two weeks, which were still obviously different from those in the sham-operated group （P 〈 0.05）. ② The HE and Nissl stained brain tissue section showed that there was nerve cell proliferation at the infarcted cortex in the experiment group, the density was higher than that in the control group, plenty of aggregative or scattered cells could be observed at the site where needle was inserted for transplantation, the cells migrated directively towards the area around them, the cerebral vascular walls were wrapped by plenty of cells; In the control group, most of the cortices were destroyed, karyopyknosis and necrosis of neurons were observed, normal nervous tissue structure disappeared induced by edema, only some nerve fibers and glial cells remained.CONCLUSION： The rMSCs transplantation can obviously enhance the motor function and the abilities of learning and memory in rat models of cerebral infarction.

Therapy with bone marrow cells reduces liver alterations in mice chronically infected by Schistosoma mansoni

AIM： To investigate the potential of bone marrow mononuclear cells （BM-MCs） in the regeneration of hepatic lesions induced by Schistosoma mansoni （S.mansoni） chronic infection. METHODS： Female mice chronically infected with S.rnansoni were treated with BM-MCs obtained from male green fluorescent protein （GFP） transgenic mice by intravenous or intralobular injections. Control mice received injections of saline in similar conditions, Enzyme-linked immunosorbent assay （ELISA） assay for transforming growth factor-beta （TGF-β）, polymerase chain reaction （PCR） for GFP DNA, immunofluorescence and morphometric studies were performed. RESULTS： Transplanted GFP^＋ cells migrated to granuloma areas and reduced the percentage of liver fibrosis. The presence of donor-derived cells was confirmed by Fluorescence in situ hybridization （FISH） analysis for detection of cells bearing Y chromosome and by PCR analysis for detection of GFP DNA. The levels of TGF-β, a cytokine associated with fibrosis deposition, in liver fragments of mice submitted to therapy were reduced. The number of oval cells in liver sections of S.mansoni-infected mice increased 3-4 fold after transplantation. A partial recovery in albumin expression, which is decreased upon infection with S.mansoni, was found in livers of infected mice after cellular therapy. CONCLUSION： In conclusion, transplanted BMCs migrate to and reduce the damage of chronic fibrotic liver lesions caused by S.mansoni.

EFFECTS OF BLOOD TRANSFUSION ON BONE MARROW TRANSPLANTATION IN RATS WITH RADIATION-BURN COMBINED INJURY

The effects of pre-irradiation blood transfusion(BT)on survival rateof radiation-burn combinedly injured rats receiving bone marrow transplantation(BMT) were studied. It was found that after 9-11 Gy of radiation was given, the 90-daysurvival rate of the rats receiving BT(72%) and BMT was significantly higher than thatof those receiving BMT only(42%)(P<0.01).In those rats surviving over 100 days,cells of donor type could be found. In the first 30 days of surviving, the number of Tcells was significantly higher in the BMT alone group than in the group of BMT plusBT, but no difference In restoration of B cell was revealed. The findings suggest that BTcould promote the recipient's tolerance to BMT. The effects of BT on BMT are similarto those on skin grafting.

Effect of bone marrow stromal cell transplantation to the hippocampal CA1 region on electroencephalographic activity in epileptic rats

BACKGROUND： Animal experiments have confirmed that bone marrow stromal cell （BMSC） transplantation can serve as a treatment for epilepsy. OBJECTIVE： BMSCs derived from green fluorescent protein （GFP） mice were transplanted into the hippocampal CA1 region of epileptic rats. The aim of the study was to record electroencephalogram （EEG）, analyze survival and migration of BMSCs, and validate the effect of BMSC transplantation for the treatment of epilepsy. DESIGN, TIME AND SETTING： A randomized block design experiment was performed at the Institute of Neuroscience, Kunming Medical College from March 2005 to February 2006. MATERIALS： Homozygous C57BL/6CrSlcTgN （acr-EGFP） OsbC 14-Y01-FM 131 mice, 8-12 weeks of age, were selected for preparation of cell suspension. Sprague Dawley rats were selected for establishing epilepsy models. METHODS： Rats were randomly divided into 4 groups： control （n = 8）, model （n = 8）, normal saline （n = 24）, and BMSC （n = 24）. In the model, normal saline, and BMSC groups, epilepsy was established with penicillin （3 × 10^7 U/kg i.p. ×7 days）. Rats in the BMSC group received a BMSC suspension derived from green fluorescent protein mice into the fight hippocampal CA1 region. Rats in the vehicle control group were injected with the same volume of normal saline into the hippocampal CA1 region. MAIN OUTCOME MEASURES： The electroencephalogram was used to monitor brain activity. Survival and migration of the transplanted BMSCs was observed using fluorescence microscopy at 1, 2, and 4 weeks after transplantation. RESULTS： In BMSC group, fluorescent cells were observed at the transplantation site and in the adjacent tissue, as well as in the tissue surrounding the needle tract, indicating the migration of implanted cells. Fluorescent cells were not detected in the vehicle control group. The electroencephalogram of the control animals exhibited 7-9 Hzα waves, with a wave amplitude 〈 50 μV. In the model and vehicle control groups random spike-and-wave discharges of the sharp spike-sharp low wave type were observed. EEG amplitudes were significantly smaller in the BMSC group, compared with the model and vehicle control groups. CONCLUSION： Following transplantation, BMSCs survived and migrated to the injury region of the epileptic rat brain and alleviated epileptic seizures.

Effect of Ligustrazine on the Expression of LFA-1, ICAM-1 Following Bone Marrow Transplantation in Mice

Summary: The effects of ligustrazine on the expression of LFA-1, ICAM-1 in bone marrow tissue and the mechanism promoting hematopoietic reconstitution following bone marrow transplantation (BMT) were investigated. The 150 mice were randomly divided into 3 groups: normal group, saline group and ligustrazine group. The normal group received no treatment, while in the saline group and ligustrazine group, the mice were subjected to normal saline (0.2 ml, twice a day) and ligustrazine (0.2 ml, twice a day) respectively through a gastric tube. At the 7th, 14th, 21st and 28th day after BMT, survival rate, colony forming unit of spleen (CFU-S), peripheral blood cells and bone marrow mononuclear cells (BMMNC) were measured, histological changes in bone marrow tissue were observed and the expression level of LFA-1, ICAM-1 was detected. In ligustrazine group CFU-S counts on the 10th day and the peripheral blood WBC, PLT, BMMNC counts, hematopoietic tissue volume as well as the expression level of LFA-1 on the 7th, 14th, 21st, 28th day after BMT were higher than in saline group (P<0.01 or P<0.05). Mature RBC volume and the expression level of ICAM-1 were significantly lower in the ligustrazine group than in the saline group (P<0.01 or P<0.05). In the ligustrazine group, fat tissue volume was higher on the 7th, 14th day after BMT (P<0.01) and was lower on the 21st, 28th day (P<0.01) after BMT than in the saline group. It was concluded that Ligustrazine could improve bone marrow microenvironment and promote hematopoietic reconstitution.

Acute GvHD and the cutaneous ultrastructural changes in mismatched bone marrow transplantation

Six patients treated with human leukocyte antigen (HLA)-mismatched bone marrow transplantation (BMT) suffered from grade I to IV acute graft-versus-host disease (aGvHD) after engrafting. Up to date, 4 patients with grade I to II GvHD have lived for over 2920, 910, 740 and 680 days, respectively. Two other patients died of grade IV hyperacute GvHD. The results seem to indicate that patients in mismatched BMT have a high incidence of aGvHD within a month. The severity of aGvHD is positively correlated with the degree of HLA mismatching. The higher the degree of mismatch of HLA, the earlier and the more severe the aGvHD occurrs. The cutaneous lesion of the patient with GvHD is severe and of ten complicated by mucositis. Lethal hyperacute GvHD must be considered when a patient shows following signs at beginning: (1) The symptoms appear early (within 2weeks) ;(2) peripheral white blood cell count does not recover (<0. 5×109/L) to normal; and (3) high fever persists. In the epidermal ultrastructure of patients, besides acantholysis, autophagic degeneration of keratinocytes,and satellite cell dyskeratosis, there were scattered necrotic keratinocytes, breaking and thickening of basal membrane and presence of a lot of pigment in the intercellular space. These imply that the ultrastructural damages in the skin of patients with aGvHD after mismatched transplantation are more severe than after matched ones.

Study on the Effect of Ligustrazine on Hematopoietic Reconstitution in Bone Marrow Transplantation Mice

To explore tile effects of ligustrazine on hematopoietic reconstitution and its mechanism after bone marrow transplantation (BMT), the allogenic BMT mice were given intra-abdominal injection of 2,mg ligustrazine twice a day. On the 1st, 7th, 14th, and 28th day after BMT, peripheral blood cells and bone marrow nuclear cells (BMNC) were counted, and the histological features were evaluated. On the 7th, 14th, 21st day after BMT, CXCR4 expression on the BMNC was assayed. The results showed that peripheral blood cell counts and BMNC counts in ligustrazine-treated group on the 7th, 14th, 28th day were higher than those in BMT group (P<0. 01 or P<O. 05). The percentage of hematopoietic tissue volume, fat tissue hyperplasia and congestion and dilation degree of microvessel in ligustrazine-treated group on the 7th, 14th, 21st, 28th day was higher than those in BMT group. The CXCR4 expression levels in ligustrazine-treated group were higher than in BMT group (P<0.01 or P<0. 05) on the 7th and 14th day, and were lower than in BMT group on the 21st day (P<0. 01 ). It is concluded that the ligustrazine can accelerate hematopoietic reconstruction, enhance growth of hematopoietic tissues and promote the repair of microvessels. The CXCR4 expres- sion levels on BMNC may be responsible for the effect of ligustrazine.

THE STRATEGIES FOR PREVENTING AND TREATING IN-FECTION OF CYTOMEGALOVIRUS IN BONE MARROW TRANSPLANTATION

In bone marrow transplantation (BMT), cytomegalovirus (CMV) interstitial pneumonitis (IP) is one of the most dangerous complications, which has been the first important cause to lead the failure of BMT. At present, there is no effective and specific therapy for CMVIP, therefore how to prevent CMV infection effectively is a top task. From 1991 to 1996, we used comprehensive steps to prevent CMVIP in BMT, and none of 14 patients developed CMVIP. The preventing results that we achieved by using the steps were quite satisfied.