Transplantation of CTLA4Ig gene-transduced adipose tissue-derived mesenchymal stem cells reduces inflammatory immune response and improves Th1/Th2 balance in experimental autoimmune thyroiditis

✍ Scribed by Eun Wha Choi; Il Seob Shin; Hee Woo Lee; So Young Park; Ji Hyun Park; Mi Hyun Nam; Jong Sung Kim; Sang Kyu Woo; Eun Ji Yoon; Sung Keun Kang; Jeong Chan Ra; Hwa Young Youn; Sung Hwa Hong

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 627 KB
• Volume: 13
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.1531

✦ Synopsis

Abstract

Background

Autoimmune thyroiditis is one of common organ‐specific autoimmune disease. The aim of this study was to observe the effect of adipose tissue derived mesenchymal stem cells (ATMSC) and CTLA4Ig gene‐transduced ATMSC on autoimmune thyroiditis.

Methods

Experimental autoimmune thyroiditis was induced by immunization with thyroglobulin. Animals were divided into three groups: (i) a half million of human ATMSC, (ii) a half million of murine CLTA4Ig gene‐transduced human ATMSC (CTLA4Ig‐MSC), or (iii) normal saline (as control), which were administered intravenously four times within a 3‐week period. Blood and tissue samples were collected 1 week after the last cell transplantation.

Results

The absorbance of serum thyroglobulin autoantibody (TgAA) in the CTLA4Ig‐MSC group was considerably lower than those in other groups. In culture supernatant of LPS‐stimulated spleen cells, both of the MSC‐treated groups showed significantly lower absorbances of TgAA than the control. Flow cytometric analysis of spleen cells revealed a significant decrease in the proportion of CD3+ and CD11b in the CTLA4Ig‐MSC group compared to the other groups. Lymphocyte infiltration in the thyroid glands was also dramatically decreased in both of MSC‐treated groups. Cytokine analysis showed that ATMSC decreased the production of proinflammatory cytokines and improved the Th1/Th2 balance by down‐regulating Th1 cytokines.

Conclusion

Although CTLA4Ig‐MSC transplantation had better result in reduction of serum TgAA, both of ATMSC and CTLA4Ig‐MSC transplantations are promising treatments for autoimmune thyroiditis judging from the results of histopathology and cytokine analysis. They may be attractive candidates for treating organ‐specific autoimmune disease. Copyright © 2011 John Wiley & Sons, Ltd.