ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
BACKGROUND:Stromal cel-derived factor-1 has a strong chemotaxis to bone marrow mesenchymal stem cels, and both of them can promote wound healing. However, there are less studies on their correlation with skin wound healing. OBJECTIVE:To investigate the effects of stromal cel-derived factor-1 on bone marrow mesenchymal stem cels migration and skin wound repair. METHODS: Thirty SD rats were divided into five groups at random. Bone marrow mesenchymal stem cels labeled with PKH-26 were injected into the rat caudal vein. After 1 week, skin wound models were established. Then, different concentrations (1, 2, 10, 50 μg/L) of stromal cel-derived factor-1 were injected via multi-points on the skin wound. The skin wound healing was observed and recorded at 14 days after injection. The number and distribution of bone marrow mesenchymal stem cels were observed by the fluorescent staining at different time points. The pathological changes of wound tissue were observed by hematoxylin-eosin staining. The expression of colagen I and colagen III were detected by western blot assay. RESULTS AND CONCLUSION:Stromal cel-derived factor-1 at 10 μg/L could induce the largest number of bone marrow mesenchymal stem cels to the skin wound and achieve the best repair results. Stromal cel-derived factor-1 could also regulate the expression of colagen I and colagen III in the wound, and when the concentration of stromal cel-derived factor-1 was 10 μg/L, the expressions of colagen I and colagen II reached the peak. These findings indicate that the appropriate concentration of stromal cel-derived factor-1 is better to promote the migration of bone marrow mesenchymal stem cels, thereby contributing to skin wound repair.
ABSTRACT
BACKGROUND: Core decompression alone for osteonecrosis of femoral head easily causes fovea of femoral head and colapse of inner microstructure. Therefore, autologous bone is needed for filing and supporting. Moreover, bone marrow stem cel transplantation can decrease the incidence of femoral head colapse. OBJECTIVE:To discuss the clinical effects of core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cels for osteonecrosis of femoral head. METHODS: A total of 33 patients were treated by core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cels in the Fourth Department of Bone Surgery, Central Hospital Affiliated to Shenyang Medical Colege in China from December 2012 to May 2013. RESULTS AND CONCLUSION:After the treatment by core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cels, Harris hip function score increased and pain disappeared in patients with osteonecrosis of femoral head. They could do various labors. Radiographs or CT examination displayed normal femoral head in 30 hips, accounting for 79%. Pain significantly reduced. Normal or slight limp walking was found in 15 hips, accounting for 40%. There were 35 hips in patients, whose walking distance was extended, accounting for 92%. 24 hips dysfunction was improved markedly, accounting for 63%. Al results suggested that core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cels improved the local blood supply of femoral head, and played a positive role in promoting the necrotic bone absorption and bone repairing.
ABSTRACT
BACKGROUND:Human telomerase reverse transcriptase (hTERT) is the first choice for regulating the proliferation and directional differentiation, with multiple biological effects. OBJECTIVE:To observe the therapeutic effect of hTERT-transfected bone marrow mesenchymal stem cels transplantation in diabetic rats. METHODS: Bone marrow mesenchymal stem cels from Sprague-Dawley rats were culturedin vitro and transfected with retrovirus PLXSN carrying hTERT. RT-PCR was used to detect the hTERT expression in the bone marrow mesenchymal stem cels before and after transfection. Sixty male Sprague-Dawley rats were selected and equaly randomized into four groups: normal control group, transfection group, cel transplantation group, and model group. In the latter three groups, rats were injected with 45 mg/kg chain urea to establish diabetes models, and then injectedvia the tail vein with 0.2 mL hTERT-transfected bone marrow mesenchymal stem cels, 0.2 mL bone marrow mesenchymal stem cels, and 0.2 mL normal saline, respectively. RESULTS AND CONCLUSION:At 48 hours after hTERT transfection, the expression of hTERT mRNA was detected in the bone marrow mesenchymal stem cels, and mainly concentrated in the nuclei. At 14 days after transfection, the fasting glucose level in the model group was higher than that in the normal control group (P 0.05). These findings indicate that the transplantation of hTERT-transfected bone marrow mesenchymal stem cels is effective in the treatment of diabetic rats.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
BACKGROUND:Cel transplantation becomes a new approach for treatment of cerebral infarction. In recent years, bone marrow mesenchymal stem cels (BMSCs) have become an important kind of seed cels in cel transplantation. OBJECTIVE: To investigate the effect of fleabane injection combined with BMSC transplantation on S100B protein and superoxide dismutase expression in acute cerebral infarction rats. METHODS:Animal models of acute cerebral infarction were made in Sprague-Dawley rats using suture method. After successful modeling, 80 model rats were randomly divided into control group, fleabane group, BMSC group and combined group (fleabane combined with BMSC transplantation). Changes of serum S100B protein and serum superoxide dismutase levels were detected using enzyme-linked immunosorbent assay and xanthine oxidase method, respectively, before and after treatment. NIHSS neurological function scores were measured to observe neurological behavior changes in model rats. The infarct volume was measured by TTC staining. RESULTS AND CONCLUSION:At 36, 7, 14 days after treatment, S100B protein levels in the fleabane group and BMSC group were significantly lower than that in the control group, but higher than that in the combined group (P <0.05); serum superoxide dismutase levels in the fleabane group and BMSC group were significantly higher than that in the control group, but lower than that in the combined group (P < 0.05). At 1, 2, 3 weeks after treatment, NIHSS neurological function scores were ranked as folows: combined group < fleabane group and BMSC group < control group, and there was a significant difference between groups (P < 0.05). At 2 weeks after treatment, the infarct volume in the fleabane group and BMSC group was higher than that in the combined group but lower than that in the control group (P < 0.05). These findings indicate that fleabane combined with BMSC transplantation can inhibit the expression of S100B protein in rats with acute cerebral infarction, and promote the activity of superoxide dismutase, thereby playing a neuroprotective role.
ABSTRACT
BACKGROUND:Mesenchymal stem cel transplantation has a certain controversy in the treatment of liver cirrhosis, and its effects on the receptor liver structure and function need further studies. OBJECTIVE:To study the changes in liver ultrastructure, stereology parameters and liver function indexes of rat models with liver cirrhosis treated by bone marrow mesenchymal stem cel transplantation. METHODS:Rat models of liver cirrhosis were made using carbon tetrachloride and treated by bone marrow mesenchymal stem cel transplantation. Liver ultrastructure of al the rats were observed by transmission electron microscope, the stereology parameters of the hepatic sinusoid were analyzed by a stereology analysis software, and the serum liver function indexes were detected by a biochemical analyzer. RESULTS AND CONCLUSION: (1) The hepatic cels in the rat models exhibited acute hypoxia, lots of mitochondria were destroyed, and obvious karyopycnosis and capilarization of the hepatic sinusoid were found. The liver ultrastructure of rats undergoing cel transplantation was improved remarkably, the hepatic cel nucleus was nearly normal, mitochondrial sweling relieved notably and nuclear pore clogging lessened. (2) The number of hepatic sinusoids in the model group was reduced dramaticaly, but the total area and mean diameter of the hepatic sinusoid were enlarged significantly as compared with the cel transplantation and normal groups (P 0.05). These findings indicate that bone marrow mesenchymal stem cel transplantation can improve liver function and structure of rats with liver cirrhosis and lessen pathological changes of hepatic sinusoid, so it is an effective treatment for liver cirrhosis.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.