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

Abstract

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)-γ. 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-γ, 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.

Changes in inflammatory factors and prognosis of patients complicated with non-alcoholic fatty liver disease undergoing coronary artery bypass grafting

“…Likewise, Napoleão et al ( 16 ) found that the expression levels of sCD40L were significantly increased in peripheral blood within 10 min after CABG compared with those before operation, suggesting that the levels may be associated with postoperative systemic inflammatory responses. Ma et al ( 17 ) showed that the expression levels of ICAM-1 increased slightly in peripheral blood of patients in the two groups after operation, but the differences were not statistically significant. The expression level of ICAM-1 of patients in NAFLD group almost had no change.…”

Chaihulonggumulitang Shows Psycho-cardiology Therapeutic Effects on Acute Myocardial Infarction by Enhancing Bone Marrow Mesenchymal Stem Cells Mobilization

“…The transmigration of BM-MSCs requires CD106 (vascular adhesion molecule-1, VCAM-1) expression on BM-MSCs and cardiac microvascular endothelium 24 , 25 . Similarly, CD54 (intercellular cell adhesion molecule-1, ICAM-1) regulates the migration of BM-MSCs to injured tissues 26 . In our study, percentage of CD54 + and CD106 + cells declined in bone marrow on day 3 after ligation surgery in the model group.…”

Immunosuppressive Property of MSCs Mediated by Cell Surface Receptors

“…Adhesion molecules mediate the first step in cell-to-cell communication between MSCs and target cells expressed on MSCs (ICAM-1, VCAM-1, and P-selecting), which interact with corresponding receptors presented on target cells (6,44,45). As mention above, ICAM-1 is the highest expressed adhesion molecules on MSCs, so we focus on ICAM-1 to explain the role of adhesion molecules in the immunosuppression of MSCs.…”

“…Recent studies have shown that ICAM-1 has also been expressed on MSCs and functionally affected MSCs characteristics such as immunosuppression capacity (3,6,41,48). ICAM-1 may play a decisive role in the regulation of immunosuppressive properties.…”

“…Evidence suggested that the immunosuppressive properties of MSCs were mediated by direct or indirect cell-to-cell communication to educate immune cells and ultimately regulate the disease-specific microenvironment (3,4). Various surface molecules mediate direct cell-to-cell communication, such as chemokine receptors, co-inhibitory molecules, cytokine receptors, and adhesion molecules (3,(5)(6)(7). On the other hand, indirect cell-to-cell communication is achieved by extracellular vesicles secreted by MSCs, which included HGF, TSG-6, TGF-β, PGE2, IDO, IL-10, NO, HO-1, or HLA-G (4,(8)(9)(10)(11)(12)(13)(14).…”