Chinese Journal of Tissue Engineering Research ›› 2014, Vol. 18 ›› Issue (45): 7279-7284.doi: 10.3969/j.issn.2095-4344.2014.45.012

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Variation of Th1/Th2 and Terg in rheumatoid arthritis patients undergoing umbilical cord mesenchymal stem cell transplantation

Wang Li-ming1, Wang Li-hua2, Li Ming1, Bai Wen1, Zhong Zhan-qiang1, Shi Jun1, Zhou Jian-jun1, Huang Shi-gao1, Li Na2, Ji Hai-jie2, Liu Yong-jun2, Wu Ming-yuan2   

  1. 1the 323rd Hospital of PLA, Xi’an 710054, Shaanxi Province, China; 2Heze Stem Cells and Regenerative Medicine Research Center, Tianjin 300381, China
  • Online:2014-11-05 Published:2014-11-05
  • Contact: Liu Yong-jun, M.D., Professor, Heze Stem Cells and Regenerative Medicine Research Center, Tianjin 300381, China
  • About author:Wang Li-ming, Master, the 323rd Hospital of PLA, Xi’an 710054, Shaanxi Province, China
  • Supported by:

    the Military Medical Health Plan, No. CLZ12GA23

Abstract:

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.

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程


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Key words: arthritis, rheumatoid, umbilical cord, mesenchymal stem cell transplantation, T-Lymphocytes, regulatory, Th1-Th2 balance

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