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Yu X.-D.,The 323rd Hospital of PLA | Wang W.-Z.,PLA Fourth Military Medical University | Jiao J.-Y.,Industry Weapon | Zheng J.-Y.,PLA Fourth Military Medical University | Zhao Z.-W.,PLA Fourth Military Medical University
Chinese Journal of Tissue Engineering Research | Year: 2014

Background: As the potent, specific immunosuppressants emerge, the survival rate after intestinal transplantation is improved to some extent. However, the adverse effects of immunosuppressants and expensive treatment costs are not tolerable for many patients. Therefore, it is clinically meaningful to choose traditional Chinese medicine which presents immunosuppressive effects. Artesunate has immune suppression effect, reduces acute rejection following small intestine transplantation, and improves the success rate of small intestine transplantation. Objective: To observe the effect and action mechanism of artesunate in acute rejection after small intestine transplantation in rats. Methods: Allogeneic small intestine transplantation models were established in the closed group of Sprague-Dawley rats and Wistar rats, and then were randomly divided into three groups, syngenic transplantation group (SD→SD), allogeneic transplantation group (Wistar→SD), and artesunate treatment group (Wistar→SD + artesunate 60 mg/kg per day, intraperitoneal injection). Results and Conclusion: Rats in syngenic transplantation group survived for more than 10 days and they were all killed on day 10. The average survival of rats in allogeneic transplantation group and artesunate treatment group was respectively (6.73±0.58) days and (8.50±0.74) days, with significant differences between the two groups (P < 0.01). Histopathological examination showed that, there was no apparent rejection in syngenic transplantation group specimens, but mild, moderate and severe rejections in allogeneic transplantation group on days 3, 5, 7. In treatment group, some specimens had mild rejection, but appeared relatively late to a low degree. Enzyme linked immunosorbent assay results revealed that, serum interleukin-2 and interferon-gamma expression levels in allogeneic transplantation group were significantly higher than other two groups after surgery (P < 0.01), serum interleukin-2 gene expression level in treatment group was also higher than syngenic transplantation group, but there was no significant difference (P > 0.05), serum interferon-gamma expression level in treatment group was higher than syngenic transplantation group (P < 0.05). Artesunate can inhibit acute rejection after rat small intestine transplantation, and its mechanism may be related to inhibition effect on the secretion and expression of interleukin-2, interferon-gamma and other cytokines.

Wang L.-M.,The 323rd Hospital of PLA | Wang L.-H.,Heze Stem Cells and Regenerative Medicine Research Center | Li M.,The 323rd Hospital of PLA | Bai W.,The 323rd Hospital of PLA | And 8 more authors.
Chinese Journal of Tissue Engineering Research | Year: 2014

BACKGROUND: Rheumatoid arthritis is an autoimmune disease, and traditional treatment methods are difficult to effectively solve the patient's lack of immune tolerance mechanisms. With the development of stem cells in regenerative medicine, stem cell therapy has become a hot spot in the treatment of autoimmune diseases. Currently, studies on cell transplantation for the treatment of rheumatoid arthritis are rarely reported. OBJECTIVE: To study the influence of umbilical cord mesenchymal stem cell therapy on the changes of Th1/Th2 and Treg in rheumatoid arthritis patients, thereby seeking new therapies for rheumatoid arthritis. METHODS: We selected 180 cases of rheumatoid arthritis, including 27 patients as control group undergoing non-steroidal anti-inflammatory drugs and anti-rheumatic drugs and 153 patients as cell treatment group undergoing intravenous infusion of 40 mL umbilical cord mesenchymal stem cells at a density of 4×107. Dosing regimen was same in the two groups. The 76 of 153 patients accepted second cell therapy at 3-4 months after the first cell therapy. After follow-up of 3 and 6 months, clinical effectiveness evaluation (DAS28, HAQ, ACR20), rheumatoid factor, anti-CCP antibodies, T cell subsets, Th cytokine were detected; for patients with second cell therapy, T cell subsets and Treg were detected at 8 months after treatment. RESULTS AND CONCLUSION: (1) At 3 months after treatment, the DAS28, HAQ and ACR20 scores were significantly lower in the cell treatment group than the control group (P < 0.01). (2) At 3 and 6 months after cell therapy, the DAS28 and HAQ scores were significantly decreased in the cell treatment group (P < 0.01), and these scores were decreased continuously after second cell therapy (P < 0.01). (3) Interferon-γ level in cells did not change obviously at 3-6 months after treatment, but the interleukin-4 level was gradually increased at 6 months after treatment (P < 0.05). (4) The number of Treg cells was significantly increased at 3-6 months after treatment (P < 0.01), which was closely related to ACR, especially ACR70 percentage (P < 0.05); the ratio of CD4+ Treg was increased significantly at 3 months after treatment (P < 0.05), and this increasing trend was also maintained at 6 and 8 months after treatment, but there was no significant difference (P > 0.05). (5) B cell levels were significantly decreased at 6 months after treatment (P > 0.05); the rheumatoid factor value was significantly decreased at 3-6 months after treatment (P < 0.05). (6) There was no change in anti-CCP antibody and interleukin-17 levels at 3-6 months after treatment. These findings indicate that after treatment with umbilical cord mesenchymal stem cells, the Th1/Th2 tends to balance and Treg level is elevated in rheumatoid arthritis patients, which are directly related to clinical trials and symptomatic relief. Therefore, standard rheumatism medication combined with umbilical cord mesenchymal stem cell transplantation can improve immune network effects, adjust the immune tolerance and prevent illness progress in rheumatoid arthritis patients. © 2014, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.

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