Journal
CELL TRANSPLANTATION
Volume 24, Issue 11, Pages 2221-2236Publisher
SAGE PUBLICATIONS INC
DOI: 10.3727/096368914X685122
Keywords
CTLA4Ig; Autoimmune disease; Adipose tissue-derived mesenchymal stem cells; Dog; Autoimmune thyroiditis
Funding
- Samsung Biomedical Research Institute [SBRI P-A9-005/SMX1131211/SMX1140141]
- Basic Science Research Program through the National Research Foundation of Korea
- Ministry of Education, Science, and Technology [NRF-2012R1A1A2006701]
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This study aimed to identify the beneficial effects of adipose tissue-derived mesenchymal stem cells (ASCs) and ASCs that overexpress the CTLA4Ig gene (CTLA4Ig-ASCs) on established autoimmune thyroiditis and to examine changes in clinical chemistry parameters and the presence of humoral responses upon repeated long-term administration of autologous ASCs. This study also aimed to acquire desirable results in a preclinical study by using large-sized lab animals and applying ASCs that overexpress therapeutic genes. Experimental autoimmune thyroiditis was induced by immunization with thyroglobulin. Experimental dogs were divided into five groups: (i) ASC IT+IV, (ii) ASC IV, (iii) CTLA4Ig-ASC IT+IV, (iv) CTLA4Ig-ASC IV, and (v) control IT+IV (saline only), and they received intrathyroidal (IT; 10 million cells/250 ill saline per thyroid) administration one time or intravenous (IV; 20 million cells/5 ml) administration seven times within a 101-day period. Blood samples were collected every week, and thyroids were harvested on days 104-106. After serial ASC or CTLA4Ig transplantation, the levels of canine thyroglobulin autoantibodies (TgAA) in serum and the infiltration of T-lymphocytes between the follicles of the thyroid glands were decreased. The expression of FoxP3 in submandibular lymph nodes was significantly increased. Repeated long-term administration of autologous ASCs or CTLA4Ig-ASCs did not generate changes in clinical chemistry parameters or humoral responses.The TgAA test can detect autoimmune thyroiditis years before clinical signs of hypothyroidism occur. Thus, ASC and CTLA4Ig-ASC transplantation in that period can be attractive candidates to ameliorate autoimmune thyroiditis and prevent the development of hypothyroidism.
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