Repairing effects of ICAM-1-expressing mesenchymal stem cells in mice with autoimmune thyroiditis.

The aim of the present study was to determine the repairing effects of intercellular adhesion molecule (ICAM)-1-expressing mesenchymal stem cells (MSCs) in mice with autoimmune thyroiditis. Following induction of an experimental autoimmune thyroiditis (EAT) model, mice were randomly divided into the following groups (n=10 each): i) Normal control; and experimental groups that were subject to EAT induction, including ii) EAT model; and iii) primary MSC; iv) C3H10T1/2/MSC; v) C3H10T1/2-MIGR1/MSC; and vi) C3H10T1/2-MIGR1-ICAM-1/MSC, which were all administered the relevant cells. MSCs were administered via the caudal vein. A blood sample was harvested from the angular vein of each animal 28 days post-treatment and ELISA was used to determine the serum total triiodothyronine, total thyroxine (T4), thyroid-stimulating hormone (TSH), anti-thyroid peroxidase (TPOAb), anti-thyroid microsomal (TMAb) and anti-thyroglobulin (TGAb) antibodies. Hematoxylin and eosin staining was performed to evaluate injury of the thyroid gland by determining the size of the follicle, inflammatory infiltration, colloidal substance retention and epithelial injury. Reverse transcription-quantitative polymerase chain reaction was performed to determine the mRNA expression of interleukin (IL)-4, IL-10, IL-17 and interferon (INF)-. Western blot analysis was performed to determine the expression of p38 mitogen-activated protein kinase (p38) and extracellular signal-regulated kinase (ERK). To observe cellular migration in vivo, mice were divided into the following groups, (n=10 each), which were subject to EAT induction: i) CM-DiI-labeled primary MSC; ii) CM-DiI-labeled C3H10T1/2/MSC; iii) CM-DiI-labeled C3H10T1/2-MIGR1/MSC; and iv) CM-DiI-labeled C3H10T1/2-ICAM-1/MSC, which were all administered the relevant cells via the caudal vein. C3H10T1/2-ICAM-1/MSCs were able to ameliorate the expression of T4, TSH, TPOAb, TMAb and TGAb in vivo, attenuate thyroid follicle injury and decrease the splenic index in mice. They were also able to ameliorate the mRNA expression of IL-4, IL-10, IL-17 and INF-, and the modulation of the P38 and ERK-signaling pathways in the mouse spleen. Furthermore, ICAM-1 overexpression was able to modulate the nesting of MSCs in the thyroid gland and lung. These findings suggest that C3H10T1/2-ICAM-1/MSC may affect the differentiation, proliferation and migration of immunocytes through modulating the p38 and ERK signaling pathways, and that ICAM-1 may modulate the immunoregulatory effects of MSCs by affecting the migration of MSCs in vivo.