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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: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: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: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: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.
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BACKGROUND:Due to the different transplantation time after myocardial infarction, the homing ability of bone marrow mesenchymal stem cels to damaged tissues as wel as the repairing role wil be very different. OBJECTIVE:To explore the optimal window time for the homing of bone marrow mesenchymal stem cels to the myocardial tissue after myocardial infarction. METHODS: Eighteen Chinese miniature pigs were modeled by the ligation of left anterior descending coronary artery. BrdU-labeled bone marrow mesenchymal stem cels were injectedvia the coronary artery at 1 day, 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks after modeling, respectively. Then, the animals were kiled at 3 days after cel transplantation to detect the home of bone marrow mesenchymal stem cels in the infarct zone. RESULTS AND CONCLUSION:BrdU-labeled positive cels with brown nuclei were visible at 1 day, 3 days, 1 week, 2 weeks, 3 weeks, and 4 weeks after myocardial infarction, especialy at 1 week after myocardial infarction (P < 0.05). It indicates that the best homing window for bone marrow mesenchymal stem cels was at week after myocardial infarction, when the stem cel transplantation is given to be able to promote myocardial repair.
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BACKGROUND:Bone marrow mesenchymal stem cels have a therapeutic effect on acute lung injury, but the mechanism is unclear. If the mechanism is understood, the majority of patients with acute lung injury can obtain a benefit. OBJECTIVE:To explore the possible mechanism underlying bone marrow mesenchymal stem cels in the treatment of acute lung injury with sepsis in rats. METHODS: (1) Thirty-six adult Wistar rats were randomly divided into three groups, sham operation group (sham group), sepsis group and bone marrow mesenchymal stem cels group (cel treatment group). In the sepsis and cel treatment groups, animal models of sepsis with acute lung injury were established by cecal ligation and puncture, while in the sham group, the cecum was not ligated and punctured. Then, 1 mL normal saline was injected via the femoral vein in the sepsis and sham groups, and 1 mL bone marrow mesenchymal stem cel suspension (1×109/L) was injected into the cel treatment group. After 6 hours, interleukin 10 and macrophage inflammatory protein-2 levels in serum were measured in the three groups. Lung tissues were taken for pathological observation using hematoxylin-eosin staining. (2) Rat alveolar macrophages were obtained by bronchoalveolar lavage, seeded into 24-wel culture plates, and divided into three groups: control group (group A), sepsis model group (group B) and intervention group of bone marrow mesenchymal stem cels (group C). Normal saline, septic plasma, and co-intervention of septic plasma and mesenchymal stem cels were used in the groups A, B, C, respectively. Then, cels in the three groups were cultured in a 5% CO2 incubator at 37℃ for 1 hour. After that, alveolar macrophages were taken to detect whether nuclear factor-κB (P65) protein entered into the nucleus using laser scanning confocal microscopy. RESULTS AND CONCLUSION: (1) The results of animal experiments showed that compared with the sham group, the macrophage inflammatory protein-2 levels in the sepsis group and cel treatment group were significantly increased (P 0.05); inflammatory cel infiltration, interstitial pulmonary edema and pulmonary hemorrhage existed in the sepsis and cel treatment groups, but these symptoms were significantly reduced in the cel treatment group compared with the sepsis group. (2) Results from cel experiments showed that compared with the group A, in group B and group C, the number of nuclear factor-κB (P65) proteins into the nucleus was significantly higher (P < 0.05), but it was lower in the group C than the group B (P < 0.05). These findings indicate that bone marrow mesenchymal stem cels in acute lung injury with sepsis can regulate nuclear factor-κB (P65) protein of alveolar macrophages into the nucleus, reduce expression of macrophage inflammatory protein-2, and thereby play a protective role in the lungvia reducing neutrophil infiltration. Temporarily, this study cannot explain whether bone marrow mesenchymal stem cels have an effect on interleukin 10.
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BACKGROUND:There are most single-center studies about bone marrow stem cels applied to treat decompensated cirrhosis, but the therapeutic results are not ideal. It is possibly related to aging, physical weakness, poor bone marrow hematopoietic function, less available number of stem cels and feeble ability of regeneration and proliferation in liver cirrhosis patients. Umbilical cord mesenchymal stem cels are characterized of easy to obtain, wide source and weak immunogenicity. Co-transplantation of bone marrow stem cels and umbilical cord mesenchymal stem cels may improve the therapeutic effects on decompensated cirrhosis patients. OBJECTIVE:To investigate the efficacy and safety of co-transplantation of umbilical cord mesenchymal stem cels and bone marrow stem cels on decompensated cirrhosis.METHODS:Thirty-two decompensated cirrhosis patients were randomly divided into two groups: in stem cel group, 13 patients received co-transplantation of umbilical cord mesenchymal stem cels and bone marrow stem cels based on regular medical treatment; in control group, 19 patients only underwent the regular medical treatment. Al the patients were folow-up for 1 year. Alanine aminotransferase, albumin, total bilirubin, prothrombin time, Child-Pugh score and Model for End-Stage Liver Disease score, 1-year survival rate, Quality of Life score and adverse reactions related to stem cel therapy were observed and recorded in the two groups at 4, 12, 52 weeks after treatment. RESULTS AND CONCLUSION:At 4, 12, 52 weeks after treatment, improvements in the liver function, prothrombin time, Child-Pugh score and Model for End-Stage Liver Disease score were found in the two groups, but there was no difference between the two groups (P > 0.05). At 4 weeks after transplantation, the clinical symptoms and Quality of Life score in the stem cel group were significantly improved, which were better than those in the control group (P 0.05). In addition, the 1-year survival rate showed no difference between the two groups, and no severe adverse reactions related to stem cel therapy occurred during the folow-up. Co-transplantation of umbilical cord mesenchymal stem cels and bone marrow stem cels is safe and effective to improve the clinical symptoms of decompensated cirrhosis patients. However, further studies with larger samples are warranted to better clarify the co-transplantation effects.
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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.
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BACKGROUND:Studies have shown that the main functions of mesenchymal stem cels include direct participation in wound healing, growth factor secretion, promoting angiogenesis, immune regulation and inflammation, anti-oxidative stress, which can be used to treat a variety of acute and chronic diseases. OBJECTIVE:To review advances in mesenchymal stem cels in the inflammatory immunomodulation. METHODS: A computer-based search of Wanfang, CNKI and PubMed databases was performed for articles concerning advances in mesenchymal stem cels in the inflammatory immunomodulation published from January 2005 to August 2015. The search terms were “stem cels, mesenchymal stem cels, immune regulation, inflammation, immune cels, inflammatory factors, treatment” in Chinese and English, respectively. Finaly, 40 articles were included in result analysis. RESULTS AND CONCLUSION:Because of their immunomodulation and muti-directional differentiation, mesenchymal stem cels garner increasing attentions. In addition, mesenchymal stem cels can be harvested from different tissues and have goodin vitroamplification capability, which have a broad prospect in the clinical use, including tissue repair and anti-inflammation. As the most promising cels used clinicaly, mesenchymal stem cels show their superiority in the treatment of many diseases, especialy in inflammations induced by immune modulation imbalance. We believe that mesenchymal stem cels wil play an important role in the future cel biotherapy.
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BACKGROUND:After articular cartilage injury, the injured cartilage almost has no self-healing ability. Articular cartilage injury repair has been always a difficulty in clinical work. OBJECTIVE:To explore the types and biological characteristics of stem cels for articular cartilage repair and to ensure the role and relative merits of stem cel transplantation in articular cartilage repair. METHODS:PubMed and CNKI were retrieved by the first author for relevant articles published from 1998 to 2015 using the keywords of “articular cartilage injury, mesenchymal stem cels, regeneration” in English and Chinese, respectively. Finaly, 47 articles were included in result analysis. RESULTS AND CONCLUSION: Stem cel therapy is the most effective method for repair of articular cartilage injury. Mesenchymal stem cels from bone marrow, adipose and umbilical cord have strong chondrogenic and cloning capacities. Bone marrow mesenchymal stem cels have a stronger differentiation potential, and can be used for repair of cartilage injury. Umbilical cord-derived mesenchymal stem cels have a low tumorigenicity. Adipose-derived stem cels can proliferate and grow faster. Stem cels combined with natural carrier materials, such as colagen, gelatin, fibrin and alginate, can promote cel adhesion, differentiation and proliferation, in order to build an effective tissue engineered cartilage for repair of articular cartilage defects.
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BACKGROUND:Reconstruction of damaged brain tissue through cel transplantation has become a new way to treat cerebral infarction. In recent years, bone marrow mesenchymal stem cels have become the new darling in cel transplantation therapy. OBJECTIVE:To investigate the effect of ginkgo-damole injection combined with bone marrow mesenchymal stem cel transplantation to improve the neurological function of acute cerebral infarction rats and its mechanism. METHODS:Animal models of middle cerebral artery occlusion were made in rats using suture method, and then 60 rat models were randomly divided into control group, cel transplantation group and combination group. The control group was given intravenous injection of PBSvia the tail vein; the cel transplantation group was given intravenous injection of bone marrow mesenchymal stem cel suspension (2.5×109/L) via the tail vein; the combination group was given intravenous injection of bone marrow mesenchymal stem cel suspension (2.5×109 /L) and ginkgo-damole injection (2 mL/kg, once a day, totaly 5 days)via the tail vein. Modified neurological severity scores were recorded at 1, 3 days and 1, 2 weeks after transplantation. At 2 weeks after transplantation, expressions of brain-derived neurotrophic factor and growth associated protein 43 in the brain were detected using RT-PCR; cel apoptosis detected using MTT assay; BrdU positive cels counted using immunohistochemistry method. RESULTS AND CONCLUSION:There were no differences in the modified neurologic severity scores among the three groups at 1, 3 days after transplantation (P > 0.05), but the modified neurological severity scores in the combination group were lower than those in the cel transplantation group and control group at 1, 2 weeks after transplantation (P < 0.05). The expressions of brain-derived neurotrophic factor and growth associated protein 43 in the brain were significantly higher in the combination group than the other two groups at 2 weeks after transplantation (P < 0.05); compared with the other two groups, the number of apoptotic cels was less but the number of BrdU positive cels was higher in the combination group (P < 0.05). These findings indicate that the combination of ginkgo-damole injection and bone marrow mesenchymal stem cel transplantation can increase the expressions of brain-derived neurotrophic factor and growth associated protein 43 in the brain, inhibit cel apoptosis and improve neurological function in rats with cerebral infarction.