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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:Conditioned medium from mesenchymal stem cels (MSC-CM) may represent a promising alternative to MSCs transplantation. Previous studies have shown that inflammatory activation can strengthen the multiple biological potencies of MSCs; however, normal MSCs with insufficiency of immunocompetence and migration ability are not effective for tissue damage repair. OBJECTIVE:To investigate differential effects of MSC-CM with and without inflammatory activation on radiation-induced intestinal injury.METHODS:MSCs from the bone marrow of SD rats were separated, cultured and identified, and then co-cultured with non-irradiated IEC-6 or irradiated IEC-6 in a transwel system for 24 hours. Then, MSCs with inflammatory activation were cultured alone for another 48 hours. After that, the supernatant was colected as non-activated MSC-CM (MSC-CMNOR) and MSC-CM under radiation-induced inflammatory condition (MSC-CMIR). Rats were exposed to 14 Gy whole abdominal irradiation and randomly divided into four groups: control group, radiation injury group (DMEM/F12), MSC-CMNOR group and MSC-CMIR group. Continuous administration was givenvia tail vein and intraperitoneal implantation of Alzet microosmotic pumps. Intestinal samples were colected at 1, 3, 7 days after radiation for analysis of short circuit variation, at 3 days after radiation for analysis of intestinal epithelium ultrastructure, and at 1, 3, 5, 7, 14 days after radiation for histological observation of the intestinal epithelium using hematoxylin-eosin staining. Blood samples were colected at 1, 3, 7 days after radiation for analysis of serum xylose levels. In addition, the survival state and survival time of rats were observed and recorded. RESULTS AND CONCLUSION: The short circuit variation responding to electrical field stimulation was significantly reduced at al frequencies, but it was significantly improved in the MSC-CMIR group. Similarly, the intestinal absorption (serum xylose levels) was also significantly impaired by irradiation, but improved by delivery of MSC-CMIR (P < 0.05). At 3 days after MSC-CMIR infusion, the intestinal epithelium exhibited an increase in crypt size and vilous length (P < 0.05). Under the electron microscope, a reduction in intestinal microvili and open tight junctions in irradiated intestinal epithelium was found, and the intestine from rats treated with MSC-CMIR had more obvious tight junctions. In addition, treatment with MSC-CMIR dramaticaly improved the survival rate and mean survival time of irradiated rats as compared to those treated with DMEM/F12 or MSC-CMNOR (P < 0.05). Taken together, the present study demonstrated that MSC-CMIR , but not non-activated MSC-CM, improves the structural and functional restoration of the smal intestine after radiation-induced intestinal injury.
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BACKGROUND:It has been demonstrated to be effective for the improvement of heart function after acute myocardial infarction with intravenous or intramyocardial administration of bone marrow mesenchymal stromal cels. However, little is known regarding the effect of the combination of intravenous and intramyocardial administration of mesenchymal stromal cels on the heart function of a chronic myocardial infarction model. OBJECTIVE:To study the effect of intravenous and intramyocardial administration of bone marrow mesenchymal stromal cels on the heart function of a rat chronic myocardial infarction model and the relevant mechanism. METHODS:Bone marrow mesenchymal stromal cels isolated from Lewis rats were expandedex vivo. BrdU-labeled bone marrow mesenchymal stromal cels (3×106) were administeredvia the femoral vein and the myocardial surface respectively into rat models of chronic myocardial infarction in cel transplantation group. The equal volume of PBS was injected into the same place in control group. Four weeks after injection, echocardiography was performed to evaluate the heart function, and then the heart tissues were harvested for immunohistochemistry examination. The total blood vessel density in the scar area was evaluated. RESULTS AND CONCLUSION:At 4 weeks after cel implantation, the left ventricular function was not improved in the two groups. The immunohistochemistry staining showed that (1) the mesenchymal stromal cels in the myocardium did not differentiate to myocardial cels; (2) there was no significant difference in the total blood vessel density in the scar area between the cel transplantation and control groups. Taken together, the combined intravenous and intramyocardial administration of bone marrow mesenchymal stromal cels cannot improve heart function in a rat chronic myocardial infarction model.
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BACKGROUND:There are no available therapies for spinal cord ischemia-reperfusion injury, and stem cel transplantation is a focused topics. OBJECTIVE:To observe the therapeutic effect of hypoxia-inducible facotr-1α gene-modified umbilical cord blood mesenchymal stem cels (UC-MSCs) transplantedvia the infrarenal abdominal aorta on spinal cord ischemia-reperfusion injury in rats. METHODS:Thirty adult female Sprague-Dawley rats were randomly divided into three groups, with 10 rats in each group. The infrarenal abdominal aorta of rats was occluded surgicaly for 1 hour, and then the spinal cord reperfusion was restored. At 2 hours after reperfusion, 1 mL of 10% PBS, UC-MSCs suspension and hypoxia-inducible factor-1α-modified UC-MSCs suspension was injectedvia the infrarenal abdominal aorta, respectively, in the three groups. At 1, 6, 12 days after injection, Basso-Beattie-Bresnahan scores were recorded and western blot assay was used to detect hypoxia-inducible factor-1α protein expression in the spinal cord. The motor-evoked potential was determined at 12 days after injection. RESULTS AND CONCLUSION: Compared with the control group, the Basso-Beattie-Bresnahan scores were significantly higher (P < 0.05), the expression of hypoxia-inducible factor-1α protein in the spinal cord tissue was significantly increased (P < 0.05), the motor-evoked potential latency was shortened (P < 0.05) and the amplitude was increased (P< 0 .05) in the untransfected group and transfection group. Compared with the untransfected group, the Basso-Beattie-Bresnahan scores were significantly higher (P < 0.05), the expression of hypoxia-inducible factor-1α protein in the spinal cord tissue was significantly increased (P < 0.05), the motor-evoked potential latency was shortened (P < 0.05) and the amplitude was increased (P < 0 .05) in the transfection group. Above al, umbilical cord blood mesenchymal stem cel transplantation modified by hypoxia-inducible factor 1α has better effects on spinal cord ischemia-reperfusion injury.
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BACKGROUND:Chemotherapy drugs can damage the ovarian function in women of childbearing age, and even lead to premature ovarian failure. Therefore, to improve and restore the ovarian function in patients has become an important issue. OBJECTIVE:To explore the therapeutic effect and feasibility of bone marrow mesenchymal stem cel therapy against chemotherapy-induced ovarian damage. METHODS:Rat models of chemotherapy-induced premature ovarian failure were established, and injected with PKH26-labeled bone marrow mesenchymal stem cels. At 15, 30, 45, 60 days after cel transplantation, five rats were selected respectively to detect folicle-stimulating hormone and estradiol levels, and then, the rats were kiled to take the right ovary for pathological examination. The number of ovarian folicles was detected under light microscope. At 30 days after cel transplantation, another two rats were selected to mate with male rats to observe the difference in the reproductive activity. RESULTS AND CONCLUSION:Four of 22 rats (18%) gradualy recovered their estrous cycle after cel transplantation, with the decreased folicle-stimulating hormone level and increased estradiol level. Moreover, the number of folicles was reduced. Al of these indicated that the ability to have children in rats was not damaged.These experimental findings suggest that bone marrow mesenchymal stem cels can partialy improve the ovarian function of rats under chemotherapy.