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B-cell lymphoma is a heterogeneous group of disorders involving malignant proliferation of B lymphocytes, accounting for approximately 85%of non-Hodgkin lymphoma. Combined use of rituximab and chemotherapy remarkably improves the survival of pa-tients with B-cell lymphoma. Despite the increase in treatment response, some patients suffer relapsed or refractory lymphoma. Nu-merous novel treatment options have been developed in pre-clinical and clinical practice, including targeted therapies, auto-hemato-poietic stem cell transplantation, cellular immunotherapy, and radioimmunotherapy. This review describes recent advances in B-cell lymphoma treatment and discusses future perspectives.
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BACKGROUND:How to avoid denervated muscular atrophy is a key factor to improve the therapeutic efficacy on peripheral nerve injuries. OBJECTIVE:To study the effect of basic fibroblast growth factor (bFGF) gene-transfected bone marrow mesenchymal stem cels against denervated muscle atrophy. METHODS: bFGF genes were transfected into rat bone marrow mesenchymal stem cels using viral transfection method, and then MTT, immunohistochemical staining, hematoxylin-eosin staining, RT-PCR, western blot, and ELISA methods were used to detect the transfection efficiency and product expression. Thirty-two Sprague-Dawley rats were selected to make animal models of sciatic nerve injury, and subjected to multi-point intramuscular injection of bFGF-transfected bone marrow mesenchymal stem cels (experimental group) or cel culture fluid (control group). At 2, 4, 6, 8 weeks after transfection, the gastrocnemius muscle tissues were harvested to detect action potential, residual wet weight, and cross-sectional area of muscle fibers. RESULTS AND CONCLUSION:The bFGF gene was successfuly transfected into bone marrow mesenchymal stem cels using the viral transfection method. The residual wet weight, cross-sectional area and residual action potential of the gastrocnemius muscle were significantly better in the experimental group than the control group (P < 0.05). These findings indicate that bFGF gene-transfected bone marrow mesenchymal stem cels transplanted into the denervated muscle can retard the development of muscle atrophy. Cite this article:Yu N, Wang YS, Qi CP.Application of basic fibroblast growth factor gene-transfected bone marrow mesenchymal stem cels in denervated muscle atrophy. Zhongguo Zuzhi Gongcheng Yanjiu. 2016;20(1):89-94.
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BACKGROUND:Choosing an effective means to label and trace the distribution, differentiation and migration of celsin vivo help to further explore the specific mechanism of cels that exert a therapeutic effect. OBJECTIVE:To understand the migration and localization of BrdU-labeled human umbilical cord mesenchymal stem cels in brain injury model rats. METHODS:Human umbilical cord blood samples were obtained, and the isolation of human umbilical cord mesenchymal stem cels was carried out. The primary and passage culture were performed. The phenotype of cels was detected by flow cytometry. Passage 3 human umbilical cord mesenchymal stem cels were labeled using BrdU, and the cel proliferation was detected using MTT method. BrdU-labeled cels were injected into brain injury ratsvia the tail vein. At 14 days after transplantation, brain tissues in the injury region were cut into sections and the migration and location of the umbilical cord mesenchymal stem cels were observed under inverted fluorescence microscope. RESULTS AND CONCLUSION: Cel surface specific markers CD45 and CD34 were detected by flow cytometry, but the cels could not express CD44, CD105 and CD29. Based on the cel growth curve, the cels came into a conditioning period at 1-3 days of seeding and came into a logarithmic phase at 3-5 days. BrdU-positive cels were visible at the injury region after 14 days, indicating that in the rats, transplanted human umbilical cord mesenchymal stem cels migrated from the peripheral blood to the site of brain injury to achieve the effective repair of injured parts. Cite this article:Liu HL, Liu ZJ, Chen XB, Hu WZ, Ding BQ. Migration and localization of umbilical cord mesenchymal stem cels implanted into brain injury model rats. Zhongguo Zuzhi Gongcheng Yanjiu. 2016;20(1):31-35.
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BACKGROUND:Diabetic lower limb ischemia is prone to involve distal lower limb arteries, and a conventional treatment is often unable to obtain the ideal effect. OBJECTIVE:To investigate the effect and safety of umbilical cord blood stem cel transplantation in the treatment of diabetic lower limb ischemia. METHODS: A diabetic rat model of lower limb ischemia was established, and along the femoral artery, five points were selected for injection of human umbilical cord mesenchymal stem cel suspension, 20 μL per point. At 1, 2, 4 weeks after transplantation, transcutaneous oxygen pressure, vascular density and vascular endothelial growth factor level in the ischemic region, and incidence of adverse reactions were recorded. RESULTS AND CONCLUSION:At 1, 2 and 4 weeks after transplantation, the transcutaneous oxygen pressure, vascular density and vascular endothelial growth factor level in the ischemic region were found increasing, which were significantly different from those before transplantation (P < 0.05). At different time after transplantation, al animals had no inflammatory reactions such as skin bleeding and dermatitis, and local red, sweling, hot, pain, and had no tumor-like growth in organs. These findings indicate that umbilical cord blood stem cel transplantation can safely and significantly improve symptoms of diabetic lower limb ischemia, which has certain application feasibility. Cite this article:Xie LH, Xing L, Zheng H. Feasibility of umbilical cord blood stem cel transplantation for the treatment of diabetic lower limb ischemia. Zhongguo Zuzhi Gongcheng Yanjiu. 2016;20(1):78-82.
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BACKGROUND:Adipose-derived mesenchymal stem cels are a kind of pluripotent stem cels that have the potential of self-renewal and proliferation, and have low immunogenicity and immunomodulatory role. OBJECTIVE:To study the effects of adipose-derived mesenchymal stem cels on T cel immune status of alergic rhinitis mouse models. METHODS:Sixty mice were randomly assigned into six groups (sensitized/chalenged/treatment): experimental group 1 was given ovalbumin/ovalbumin/high-dose adipose-derived mesenchymal stem cels, experimental group 2 given ovalbumin/ovalbumin/low-dose adipose-derived mesenchymal stem cels, experimental group 3 given ovalbumin/ovalbumin/PBS, experimental group 4 given ovalbumin/ovalbumin/0, and experimental group 5 given PBS/PBS/0, and normal control group given no treatment. In the former five groups, intraperitoneal injection of 200 μL ovalbumin sensitizing solution or PBS was conducted for basic sensitization at days 0, 7, 14; 20 μL ovalbumin chalenging solution or PBS was given for chalenging at days 15-19. In the former three groups, 0.1 mL of high-dose, low-dose adipose-derived mesenchymal stem cels or PBS was givenviathe tail vein, respectively, at days 20-22 after sensitization and chalenge. At 48 hours after final treatment, ELISA was used to detect serum levels of interleukin-4, interleukin-6, interleukin-10 and interferon-γ, and fluorogenic quantitative PCR used to detect the mRNA expressions of these cytokines in the spleen. Migration of fluorescent-labeled adipose-derived mesenchymal stem cels in the nasal mucosa was observed under fluorescence microscope, and pathological changes of the nasal mucosa were observed through hematoxylin-eosin staining. RESULTS AND CONCLUSION:Compared with the experimental group 4, the levels of interleukin-4 and interleukin-6 in the serum and spleen were significantly lower in the experimental group 1 (P 0.05). Fluorescent-labeled adipose-derived mesenchymal stem cels could migrate into the nasal mucosa, and the number of migrated cels was notably higher in the experimental group 1 than experimental group 2. Eosinophil infiltration in the nasal mucosa was remarkably aleviated in the experimental groups 1 and 2. These findings suggest that adipose-derived mesenchymal stem cels play a non-specific immunomodulatory effect dose-dependently by regulating Th1/Th2 immune imbalances and deficiencies of Treg cels.
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BACKGROUND:The non-specific immune suppression method is generaly used for treatment of systemic lupus erythematosus, but poor prognosis, such as infection and high recurrence rate, exists. OBJECTIVE:To evaluate the therapeutic effect of bone marrow mesenchymal stem cel transplantation on systemic lupus erythematosus in mice. METHODS:Sixteen mice with systemic lupus erythematosus were equivalently randomized into control and experimental groups, or then subjected to passage 3 bone marrow mesenchymal stem cel transplantation or the equal volume of normal saline via the tail vein, respectively. Mouse urine samples were colected to detect urine protein levels by Bradford method. Blood samples from the tip of the mouse tail were extracted to detect serum anti-ds-DNS antibody concentration by radioimmunoassay. Mouse kidney tissues were taken and observed pathohistologicaly through hematoxylin-eosin staining and immunohistochemistry staining under microscope. Flow cytometry was used to detect the expression of CD4+CD25+T cels in the inner canthus blood, fresh spleen and thymus. RESULTS AND CONCLUSION:Within 10 weeks after cel transplantation, the urine protein levels in the two groups were gradualy increased, and the rising velocity was higher in the control group than in the experimental group. From the 4th to 10th week, the urine protein levels in the experimental group were significantly lower than those in the control group (P 0.05). The serum anti-ds-DNA antibody concentration in the experimental group was significantly lower than that in the control group (P < 0.05). Taken together, bone marrow mesenchymal stem cel transplantation can improve the pathological damage in systemic lupus erythematosus mice, and has a certain therapeutic effect on systemic lupus erythematosus.
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BACKGROUND:Studies have shown that bone marrow mesenchymal stem cel transplantation can improve disease conditions by reducing inflammation. OBJECTIVE:To explore the therapeutic efficacy of bone marrow mesenchymal stem cels on chronic asthma rats. METHODS: A rat model of chronic asthma was established by intraperitonealy injected and aerosolized ovalbumin. After modeling, rats were given 4×105 and 8×105 bone marrow mesenchymal stem celsvia the tail vein, respectively. Thirty days later, the lung tissues were observed pathologicaly using hematoxylin-eosin staining; RT-qPCR and ELISA methods were employed to test the changes in interleukin-10, tumor necrosis factor-α and interferon-γ levels in lung tissue and peripheral blood, respectively. RESULTS AND CONCLUSION:Rat models of chronic asthma were successfuly established after intraperitoneal injection of ovalbumin combined with aerosolized ovalbumin. After 30 days of cel treatment, the structure of lung tissues were obviously recovered, and the levels of interleukin-10, tumor necrosis factor-α and interferon-γ showed some improvement in lung tissue and peripheral blood, but there were no differences between the two groups. In conclusion, bone marrow mesenchymal stem cels show some potential role in the treatment of chronic asthma.
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BACKGROUND:There is a high morbidity after spinal cord injury, and the therapeutic strategy is limited to early surgical intervention, medication and post-treatment exercise that only can improve the motor function slightly. However, there is no effective cure method. OBJECTIVE:To study the effect of partition-type spinal cord catheter combined with bone marrow stromal stem cels on T8 spinal cord transection damage in rats. METHODS:Fifty rats were randomized into five groups (n=10 per group): group I, T8 spinal cord transection (5 mm) was made in rats with no treatment; group II, the partition-type tube was inserted into the injured site after modeling; group III, partition-type tube combined with bone marrow stromal stem cels was implanted into the injured site after modeling; group IV, partition-type tube combined with polyglycolic acid fibers was implanted into the injured site after modeling; group V, partition-type tube combined with bone marrow stromal stem cels and polyglycolic acid fibers was implanted into the injured site after modeling. RESULTS AND CONCLUSION:At 2 and 12 weeks postoperatively, Basso, Beattie and Bresnahan scores were significantly higher in the groups III and IV than the groups I, II, IV (P < 0.05). At 12 weeks postoperatively, the latency of motor evoked potential below the injury plane was significantly decreased in group V compared with groups I, II, III, IV (P < 0.05). Immunohistochemical results displayed that in the groups III and V, regenerated nerve fibers grew positively and arranged orderly among the tubes, and there was no obvious winding phenomenon. Under transmission electron microscopy, a certain number of myelinated nerve fibers were found as bridges among groups. These findings indicate that the partition-type chitosan tube combined with bone marrow stromal stem cels has a good connection with the injured spinal cord a good connection to restore part of electrophysiological properties, accelerate the axon regeneration, recover the motor function, thereby providing a new direction for the treatment of spinal cord injury. Cite this article:Zhao XW, Liu X, Yu DP, Rong H, Yu XS, Yang CS, Liu T, Zhao TB. Partition-type spinal cord catheter combined with bone marrow stromal stem cels in the repair of spinal cord transection injury in rats. Zhongguo Zuzhi Gongcheng Yanjiu. 2016;20(1):42-48.
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BACKGROUND:Bone marrow mesenchymal stem cels have low immunogenicity and can induce immune tolerance. At present, the mechanism of immune regulation of bone marrow mesenchymal stem cels is not completely understood. It has been rarely reported whether the bone marrow mesenchymal stem cels can migrate to the thymus after transplantation. OBJECTIVE:To observe the distribution and survival of bone marrow mesenchymal stem cels in the thymus of aging rats after transplantation. METHODS: Bone marrow mesenchymal stem cels cultured in vitrowere transfected by adenovirus vectors expressing green fluorescent protein. Transfected bone marrow mesenchymal stem cels were injected into the portal vein of aging rats. At days 3, 7, 14, 21 after transplantation, the survival of bone marrow mesenchymal stem cels homing to the thymus was observed under fluorescence microscope. At day 3 after transplantation, thymus tissues were taken and stained with hematoxylin-eosin for pathological observation. RESULTS AND CONCLUSION:Green fluorescent protein-labeled bone marrow mesenchymal stem cels had a strong green fluorescence at days 3 and 7 after transplantation, and the cel contour was clear. There was no significant difference in the mean absorbance values at days 3 and 7 (P> 0.05). Expression of green fluorescent protein was weakened significantly at days 14 and 21 compared with that at day 3 (P < 0.05). At 3 days after transplantation, the transplanted bone marrow mesenchymal stem cels were clearly visible in the thymus, and acute rejection was not observed. The results show that bone marrow mesenchymal stem cels can migrate to the damaged thymus tissue through the blood circulation, and can survive at least 1 week.
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BACKGROUND:Platelet-derived endothelial cel growth factor (PD-ECGF) can promote revascularization in fat transplantation. OBJECTIVE: To explore the dual effects of PD-ECGF and adipose-derived mesenchymal stem cels on the survival rate of fat grafts. METHODS:(1) Adipose-derived mesenchymal stem cels were isolated from the inguinal subcutaneous fat of New Zealand white rabbits, and then cultured. Passage 3 adipose-derived mesenchymal stem cels were divided into experimental group (Lenti-PD-ECGF-EGFP transfected adipose-derived mesenchymal stem cels), control group (Lenti-EGFP transfected adipose-derived mesenchymal stem cels) and blank group (adipose-derived mesenchymal stem cels with no transfection). (2) Lenti-PD-ECGF-EGFP transfected adipose-derived mesenchymal stem cels were cultured in DMEM complete medium, and then mixed with fat tissues as group A; adipose-derived mesenchymal stem cels with no transfection were cultured in DMEM complete medium and then mixed with fat tissues as group B; DMEM complete medium with no cels served as group C. Then, the grafts in groups A, B, C were respectively injected subcutaneously into the upper left, lower left and upper right parts of the rabbits’ black. RESULTS AND CONCLUSION:(1) In the experimental group, PD-ECGF mRNA and protein expressions were significantly higher than those in the control and blank groups (P < 0.05), and cel proliferation was also the fastest. (2) Graft weight and the number of capilaries were greater in group A than groups B and C. These findings indicate that PD-ECGF transfection of adipose-derived mesenchymal stem cels not only can continuously express the PD-ECGF protein, but also can promote the proliferation of adipose-derived mesenchymal stem cels.
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BACKGROUND:Human umbilical cord blood-derived mesenchymal stem cels are able to repair and regenerate the injured myocardium, which is a new therapy for myocardial infarctionvia transplantation. OBJECTIVE:To explore the therapeutic efficacy of intracoronary injection of human umbilical cord blood-derived mesenchymal stem cels on acute myocardial infarction in rats. METHODS:Thirty-two rats were selected to make animal models of ligation of the left anterior descending coronary, and then model rats were randomized equaly to transplantation group and model group. Human umbilical cord blood-derived mesenchymal stem cels were isolated and prepared into cel suspension. Rats in the transplantation group were subjected to transplantation of human umbilical cord blood-derived mesenchymal stem cels. RESULTS AND CONCLUSION: Human umbilical cord blood-derived mesenchymal stem cels were successfuly isolated and cultured in vitro. Compared with the model group, the microvessel density, left ventricular end-systolic pressure and ±dp/dtmax were significantly increased in the transplantation group (P < 0.05), while the left ventricular end-diastolic pressure was decreased dramaticaly (P < 0.05). Electrocardiography findings showed that the heart function of rats in the transplantation group was improved slightly. These findings indicate that human umbilical cord blood-derived mesenchymal stem cels can promote myocardial angiogenesis and improve heart function of rats with myocardial infarction.
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BACKGROUND:Bone marrow mesenchymal stem cels can be used to repair neurons, but have no ideal outcomes on nervous system injuries. OBJECTIVE:To investigate the effects of bone marrow mesenchymal stem cel transplantation combined with propofol on the hind limb function and electrophysiological changes of rats with spinal cord injury. METHODS:Eighty adult Wistar rats were selected to make animal models of spinal cord injury, and then randomized into four groups (n=20): bone marrow mesenchymal stem cel group, control group, combination group, propofol group. At 6 hours after modeling, rats in these four groups were injectedvia the tail vein with bone marrow mesenchymal stem cel suspension, cel culture medium, bone marrow mesenchymal stem cel suspension+propofol solution, and propofol solution using a 1 mL syringe, respectively. Rat motor function was assessed by Basso Beattie Bresnahan score, modified Tarlov score and inclined plane test before and at 1 day, 3 days, 1-4 weeks after modeling. Under fluorescence microscope, the survival and distribution of PKH-26-labeled bone marrow mesenchymal stem cels were observed at 4 weeks after modeling, and meanwhile, hematoxylin-eosin staining was used for pathological observation. Horseradish peroxidase tracer analysis was performed to analyze regeneration of nerve fibers, and motor and somatosensory evoked potentials were used to analyze the neurophysiological recovery of rats. RESULTS AND CONCLUSION:(1) The motor function of the rat hind limb recovered best in the combination group, better in the bone marrow mesenchymal stem cel group and propofol group, but worse in the control group. (2) There were a smal amount of nerve axon-like structures and smal syringomyelia in the bone marrow mesenchymal stem cel group and propofol group, but the combination group had more axon-like structures and no syringomyelia. In the control group, no axons but spinal cord defects and syringomyelia formed. (3) The amount of horseradish peroxidase-positive nerve fibers and the number of PKH-26 positive cels were ranked as folows: control group propofol group and bone marrow mesenchymal stem cel group > combination group, and there were significant differences between the groups (P < 0.05). (5) Amplitudes of motor and somatosensory evoked potentials were arranged as folows: control group < propofol group and bone marrow mesenchymal stem cel group < combination group, and the differences were statisticaly significant (P < 0.05). These findings indicate that both propofol and bone marrow mesenchymal stem cels can promote synaptic regeneration and improve the electrophysiological function and motor function of rats with spinal cord injury. Their combination has a better role than propofol and bone marrow mesenchymal stem cels used alone.
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BACKGROUND:With the development of surgical techniques and endovascular treatment techniques, the therapeutic efficacy on arteriosclerosis obliterans of the lower limbs has been improved greatly. As the long-term prognosis is stil not clear, how to treat arteriosclerosis obliterans of the lower limbs is stil a problem for vascular surgery. OBJECTIVE:To observe the long-term clinical efficacy of autologous bone marrow stem cel transplantation in the treatment of arteriosclerosis obliterans of the lower limbs. METHODS:Thirty-nine patients with arteriosclerosis obliterans who had undergone autologous bone marrow mesenchymal stem cels (totaly 56 times of cel transplantation) from September 2007 to July 2013 were enroled in this study. As of February 2015, the folow-up time was 7.5 years. After treatment, regular telephone folow-up about limb pain, cold sensation, intermittent claudication distance, resting ankle-brachial index and limb ulcer size and depth was done annualy; at 1 year after treatment, limb arteriography and venous blood gas analysis were reviewed. RESULTS AND CONCLUSION: Of the enroled 39 patients, 4 patients were subjected to amputation because of poor efficacy, 2 patients died of acute myocardial infarction, and 2 patients died of not timely amputation. There were 31 patients who had been folowed up for over 3 years. After treatment, the resting ankle-brachial index and limb ulcer size and depth limb pain were both improved significantly. There were significant differences in 1-year limb blood oxygen partial pressure and oxygen saturation before and after treatment, and the postoperative number of capilaries also increased significantly. These findings indicate that autologous bone marrow stem cel transplantation is a safe treatment for arteriosclerosis obliterans of the lower limbs with better and stable long-term curative effects. This method is a good choice for patients who have poor blood vessels and poor efficacy of traditional methods.
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BACKGROUND:Bone marrow stem cels combined with traditional surgery regimen can significantly improve the therapeutic effects on bone nonunion, which are considered to have an important application value. OBJECTIVE:To explore therapeutic effect of bone marrow mesenchymal stem cels on bone nonunion under micro-damage environment. METHODS:Forty New Zealand white rabbits were selected and randomized into experimental and control groups, 20 rabbits in each group. Bone marrow of the tibia was extracted to isolate and culture bone marrow mesenchymal stem cels. Passage 3 cels with the order of magnitudes of 107 were labeled by superparamagnetic iron oxide nanoparticles. A 15-mm bone defect was made at the middle of the radius of the rabbit forelimb. Bone nonunion appeared at 6 weeks after bone defects. Bone marrow mesenchymal stem cels combined with iliac particles were implanted into the bone defect of rabbits in the experimental group, and only iliac particles were implanted into the bone defect of rabbits in the control group. Within 12 weeks after implantation, the bone nonunion was observed through gross morphology, X-ray observation, and pathological observation. RESULTS AND CONCLUSION:After implantation, a remarkable calus was found in the experimental group, and the bone defect recovered gradualy until it was completely healed; in the control group, there was no calus, and the bone marrow cavity was closed and ful of granulation tissues. In the experimental group, there were actively proliferated cartilage tissues, bone particles were fused, osteoid structures appeared, and osteoblasts proliferated progressively; in the control group, poor cartilage hyperplasia was found, and there were a large amount of dead bone tissues but no fused bone particles and osteoblasts. In the experimental group, X-ray films on the defected radium showed cloudiness-like shadow, the bone marrow cavity was recanalized, and the skeleton was shaped wel; in the control group, few bone particles were absorbed, the bone marrow cavity was partly recanalized, and the injured bone was not healed with osteosclerosis. These findings indicate that under the micro-damage environment, bone marrow mesenchymal stem cels can differentiate into osteoblasts to repair bone defects-induced bone nonunion.
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BACKGROUND:Alogeneic hematopoietic stem cel transplantation (alo-HSCT) is an effective mean to cure severe aplastic anemia, and especialy haplotype transplantation is regarded as a transplantation system with Chinese characteristics, and rank at the international leading level. OBJECTIVE:To explore the patterns of haplotype alo-HSCT as a new immune tolerance method for severe aplastic anemia and to solve the transplantation rejection and graft-versus-host disease. METHODS:Twelve patients with severe aplastic anemia who underwent haplotype alo-HSCT at the Department of Hematology, General Hospital of Beijing Military Area, China from April 2013 to May 2014 were enroled. Al these patients received the new regimen of inducing immune tolerance through the application of high-dose cyclophosphamide (400 mg/m2, consecutively 3 days before transplantation; 50 mg/kg, consecutively 3 days after haplotype transplantation). RESULTS AND CONCLUSION:The median time of neutrophil recovery was 17 (13-21) days, and the median time of platelet recovery was 21 (15-31) days. After transplantation, there were one case of degree II acute graft-versus-host disease and one case of chronic graft-versus-host disease, both of which were controled. The folow-up time was 6 months at least, and the median time was 11 months. During the folow-up, one case died of rejection reaction and one case died of severe lung infection. These findings indicate that the new method of inducing immune tolerance with high-dose cyclophosphamide after transplantation for severe aplastic anemia has significant effects in reducing graft-versus-host disease and transplantation-related mortality rate.
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BACKGROUND:Studies have shown that human telomerase reverse transcriptase (hTERT) has the ability to enhance cel proliferation, maintain telomere length, prolonged cel life cultured in vitro. OBJECTIVE:To observe the effect of hTERT gene-modified bone marrow mesechymal stem cel transplantation on neural function recovery of rats with cerebral infarction. METHODS:Rat models of middle cerebral artery occlusion were established and randomized into model group, cel transplantation group and hTERT-modified cel transplantation group, with 20 rats in each group. Rats in the three groups were respectively injected via tail vein with 1 mL PBS, passage 9 bone marrow mesenchymal stem cel suspension (2.5×107/L) and hTERT-modified passage 9 bone marrow mesenchymal stem cel suspension (2.5×107/L), respectively. Modified neurological severity scores were determined before and after transplantation; RT-PCR and western blot assay were used to measure hTERT expression at gene and protein levels; TUNEL method was adopted to detect cel apoptosis in the brain. RESULTS AND CONCLUSION:hTERT-modified bone marrow mesenchymal stem cels had prolonged cel cycle, and with the increase in passage number, the cels showed good growth with no changes in morphology. The expressions of hTERT mRNA and protein were superior in the hTERT-modified cel transplantation group than the cel transplantation group, and there was a significant difference (P < 0.05). Modified neurological severity scores and number of apoptotic cels were decreased significantly in the hTERT-modified cel transplantation group compared with the other two groups (P < 0.05). These findings indicate that hTERT-modified bone marrow mesenchymal stem cels can promote neural functional recovery of rats with cerebral infarction.
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BACKGROUND:Previous studies have shown that bone marrow mesenchymal stem cels in the treatment of neurological diseases have achieved some success, which can promote neurological alterations; however, there is no breakthrough on gene and drug regulation. OBJECTIVE:To investigate the influence of ginsenosides-induced differentiation of bone marrow mesenchymal stem cels on nerve regeneration after traumatic brain injury. METHODS: A traumatic brain injury model was built in rats using hydraulic shock method, and then rat models were randomly divided into model group (traumatic brain injury group), bone marrow mesenchymal stem cel group, ginsenosides group (ginsenosides induced differentiation of bone marrow mesenchymal stem cels). At 2 weeks after transplantation, western blot assay was used to detect protein expression levels of nerve growth factor and brain-derived neurotrophic factor, immunohistochemistry assay used to detect the number of BrdU-positive cels. At 1, 3 days and 1, 2 weeks after transplantation, modified neurological severity scores were recorded. RESULTS AND CONCLUSION: The expression levels of nerve growth factor and brain-derived neurotrophic factor protein were significantly higher in the ginsenosides group than the bone marrow mesenchymal stem cel group and model group (P < 0.05). The number of BrdU positive nerve cels was also higher in the ginsenosides group than the bone marrow mesenchymal stem cel group and model group (P < 0.05). At 3 days and 1, 2 weeks after transplantation, the modified neurological severity scores in the ginsenosides group were lower than those in the bone marrow mesenchymal stem cel group and model group (P< 0.05). These findings indicate that ginsenoside-induced bone marrow mesenchymal stem cel transplantation can promote nerve regeneration in rats with traumatic brain injury, which has better outcomes than bone marrow mesenchymal stem cel transplantation alone.
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BACKGROUND:Mesenchymal stem cels can differentiate into lung parenchymal cels involved in lung injury repair, providing a new approach for the application of mesenchymal stem cels in patients with chronic obstructive pulmonary disease. OBJECTIVE:To observe the effect of bone marrow mesenchymal stem cel transplantation on the repair of airway injury in rats with chronic obstructive pulmonary disease. METHODS:Twenty-four female rats were randomized into four groups: bone marrow mesenchymal stem cel transplantation group (cel transplantation group,n=12); bone marrow mesenchymal stem cels group (cel control group,n=4); model group (n=4); healthy control group (n=4). Rat models of chronic obstructive pulmonary disease were established in the cel transplantation group and model group using fumigation+lipopolysaccharide method; and at 1 day after modeling, model rats were given 1 mL CM-Dil-labeled bone marrow mesenchymal stem cels and 1 mL PBSvia the tail vein in these two groups, respectively. In addition to tracheal injection of normal saline (300 μL) at 1 and 14 days, rats in the cel control and healthy control groups were given 1 mL CM-Dil-labeled bone marrow mesenchymal stem cels and 1 mL PBSvia the tail vein, respectively. At 1, 7, 15 and 30 days after cel transplantation, lung tissue and serum markers of al rats were detected. RESULTS AND CONCLUSION:(1) Hematoxylin-eosin staining showed that emphysema and airway injury was milder in the cel transplantation group than the model group, but severer than the cel control and healthy control groups. (2) The total number of leukocytes and neutrophils in the peripheral blood was higher in the cel transplantation group than the cel control and healthy control groups (P < 0.05); with time, the total number of leukocytes and neutrophils was decreased gradualy. (3) Compared with the cel control and healthy control groups, the interleukin-10 level in the peripheral blood was lower and the levels of tumor necrosis factor-α and granulocyte colony-stimulating factor were higher at 1 day after cel transplantation (P < 0.05). With time, in the cel transplantation group, the interleukin-10 level was increased gradualy, the level of tumor necrosis factor-α was decreased gradualy, and the level of granulocyte colony-stimulating factor was increased first and then decreased, which was highest at 7 days after cel transplantation. (4) Partial CM-Dil-positive cels were positive for CC16. Taken together, bone marrow mesenchymal stem cel transplantationvia the tail vein can improve lung injury of rats with chronic obstructive pulmonary disease, and it is involved in the repair of airway injury through differentiation into epithelial cels and immune regulation.
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BACKGROUND:Systemic lupus erythematosus (SLE) is classified into four types, and the major treatment is to tonify kidney and nourishyin, clear blood stasis and toxin by the traditional Chinese medicine (TCM). Even though, there are stil many patients with poor efficacy. Mesenchymal stem cels have the capacity of multiple differentiation, hematopoietic support and immune regulation, thus having been used for the treatment of refractory, recurrent SLE and achieving good effects. OBJECTIVE:To investigate the therapeutic effect of umbilical cord-derived mesenchymal stem cel transplantation on SLE patients with different patterns of syndromes. METHODS: Twenty-one SLE patients were clustered to four syndrome types of TCM, including heat-toxin,yin deficiency of liver and kidney,yang deficiency of spleen and kidney, andqi stagnation and blood stasis. The changes in clinical and laboratory indicators were analyzed statisticaly before and after cel transplantation. RESULTS AND CONCLUSION:The level of 24-hour proteinuria and SLE disease activity index scores in SLE patients were significantly decreased at 1, 3, 6 months after cel transplantation (P < 0.01). Umbilical cord-derived mesenchymal stem cel transplantation could significantly reduce the 24-hour proteinuria in SLE patients withyin deficiency of liver and kidney at 1, 3 and 6 months (P < 0.01), while slightly reduce the 24-hour proteinuria in SLE patients with heat-toxin andqi stagnation and blood stasis at 1, 3 months (P < 0.05) as wel as in SLE patients withyang deficiency of spleen and kidney at 1 month (P < 0.05). Additionaly, umbilical cord-derived mesenchymal stem cel transplantation could increase the serum albumin levels in al the SLE patients (P < 0.01), although the changes in patients with heat-toxin were moderate (P < 0.05). Al the SLE patients of four types had an increasing trend of their platelet counting after cel transplantation, but there was no statistical difference before and after cel transplantation. Taken together, umbilical cord-derived mesenchymal stem cel transplantation is effective for treatment of SLE, but has different therapeutic efficacy on SLE patients with different syndrome types of TCM.
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BACKGROUND:An increasing number of studies have shown that mesenchymal stem cels have the potential to treat acute kidney injury. Umbilical cord-derived mesenchymal stem cels have general characteristics of stem cels and many advantages, such as easy to isolate and culture, in vitrofast amplification, low immunogenicity and no ethical problems, which have garnered increasing attentions. OBJECTIVE:To study the repairing effects of human umbilical cord-derived mesenchymal stem cels on acute kidney injury in rats. METHODS: Thirty rats were randomized into three groups: a normal control group, a model group and a cel transplantation group. Rats in the model and cel transplantation were subjected to clamping the renal pedicles for 45 minutes, and then injected 1 mL of DAPI-labeled umbilical cord-derived mesenchymal stem cels or 1 mL of saline via the tail vein. In the normal control group, the kidney was only exposed with no treatment. At 7 days after treatment, the rats were kiled to take left kidney tissues for pathological observation under light microscope and right kidney for observation of DAPI-positive cel counting. Automatic biochemical analyzer was used to detect serum creatinine and urea ammonia levels. RESULTS AND CONCLUSION: Compared with the model group, the levels of serum creatinine and urea ammonia were significantly lower in the cel transplantation group (P < 0.05), suggesting that human umbilical cord-derived mesenchymal stem cels can improve the kidney function to a certain extent. Pathological findings showed that the pathological damage was improved more remarkably in the cel transplantation group than the model group, and the tubular necrosis index decreased significantly in the cel transplantation group. At 7 days after cel transplantation, blue fluorescent cels were scattered on renal tissue frozen sections. These results indicate that human umbilical cord-derived mesenchymal stem cels can migrate to the injured tubular epithelial tissues, and promote the repair of the injured kidney.