title: Therapeutic effects of CTLA4Ig gene-transduced adipose tissue-derived mesenchymal stem cell transplantation on established autoimmune thyroiditis.
abstract: 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 µl 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.
authors.affiliation: Laboratory Animal Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea.
authors.forename: Eun Wha
authors.initials: EW
authors.lastname: Choi
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Hee Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Jehoon
authors.initials: J
authors.lastname: Yang
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Youn
mesh_terms: D000069594:Abatacept / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use*; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D004285:Dogs; D051858:Forkhead Transcription Factors / Q000235:genetics; D007037:Hypothyroidism / Q000188:drug therapy / Q000517:prevention & control; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000473:pathology / Q000628:therapy*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D000069594:Abatacept