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

Ma,Shifeng; Chen,Xiuhui; Wang,Lihui; Wei,Ying; Ni,Yongqing; Chu,Yanan; Liu,Yuanlin; Zhu,Heng; Zheng,Rongxiu; Zhang,Yi

doi:10.3892/etm.2017.4131

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

Authors:
- Shifeng Ma
- Xiuhui Chen
- Lihui Wang
- Ying Wei
- Yongqing Ni
- Yanan Chu
- Yuanlin Liu
- Heng Zhu
- Rongxiu Zheng
- Yi Zhang
View Affiliations

Affiliations: Department of Paediatrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Department of Postgraduate Studies, Hebei North College, Zhangjiakou, Hebei 075000, P.R. China, Department of Cell Biology, Institute of Basic Medical Sciences, Beijing 100085, P.R. China
Published online on: February 16, 2017 https://doi.org/10.3892/etm.2017.4131
Pages: 1295-1302
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Chistiakov DA: Immunogenetics of Hashimoto's thyroiditis. J Autoimmune Dis. 2:12005. View Article : Google Scholar : PubMed/NCBI
2	de Vries L, Bulvik S and Phillip M: Chronic autoimmune thyroiditis in children and adolescents: At presentation and during long-term follow-up. Arch Dis Child. 94:33–37. 2009. View Article : Google Scholar : PubMed/NCBI
3	DeBoer MD and LaFranchi S: Differential presentation for children with autoimmune thyroiditis discovered because of symptomdevelopment or screening. J Pediatr Endocrinol Metab. 21:753–761. 2008. View Article : Google Scholar : PubMed/NCBI
4	Lichiardopol C and Mota M: The thyroid and autoimmunity. Rom J Intern Med. 47:207–215. 2009.PubMed/NCBI
5	Heymann WR: Chronic urticaria and angioedema associated with thyroid autoimmunity: Review and therapeutic implications. J Am Acad Dermatol. 40:229–232. 1999. View Article : Google Scholar : PubMed/NCBI
6	Cipriani P, Carubbi F, Liakouli V, Marrelli A, Perricone C, Perricone R, Alesse E and Giacomelli R: Stem cells in autoimmune diseases: Implications for pathogenesis and future trends in therapy. Autoimmun Rev. 12:709–716. 2013. View Article : Google Scholar : PubMed/NCBI
7	Oreffo RO, Cooper C, Mason C and Clements M: Mesenchymal stem cells: Lineage, plasticity, and skeletal therapeutic potential. Stem Cell Rev. 1:169–178. 2005. View Article : Google Scholar : PubMed/NCBI
8	Ding DC, Shyu WC and Lin SZ: Mesenchymal stem cells. Cell Transplant. 20:5–14. 2011. View Article : Google Scholar : PubMed/NCBI
9	Liu S, Yuan M, Hou K, Zhang L, Zheng X, Zhao B, Sui X, Xu W, Lu S and Guo Q: Immune characterization of mesenchymal stem cells in human umbilical cord Wharton's jelly and derived cartilage cells. Cell Immunol. 278:35–44. 2012. View Article : Google Scholar : PubMed/NCBI
10	Wada N, Gronthos S and Bartold PM: Immunomodulatory effects of stem cells. Periodontol 2000. 63:198–216. 2013. View Article : Google Scholar : PubMed/NCBI
11	Buschmann K, Koch L, Braach N, Mueller H, Frommhold D, Poeschl J and Ruef P: CXCL1-triggered interaction of LFA1 and ICAM1 control glucose-induced leukocyte recruitment during inflammation in vivo. Mediators inflamm. 2012:7391762012. View Article : Google Scholar : PubMed/NCBI
12	Chen JD, Xu FF, Zhu H, Li XM, Tang B, Liu YL and Zhang Y: ICAM-1 regulates differentiation of MSC to adipocytes via activating MAPK pathway. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 22:160–165. 2014.(In Chinese). PubMed/NCBI
13	Kong YC: Experimental autoimmune thyroiditis in the mouse. Curr Protoc Immunol. 15:Unit 15.72007.PubMed/NCBI
14	Prassopoulos P, Daskalogiannaki M, Raissaki M, Hatjidakis A and Gourtsoyiannis N: Determination of normal splenic volume on computed tomography in relation to age, gender and body habitus. Eru Radiol. 7:246–248. 1997. View Article : Google Scholar
15	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-tie quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
16	Nagayama Y, Horie I, Saitoh O, Nakahara M and Abiru N: CD4+ CD25+ naturally occurring regulatory T cells and not lymphopenia play a role in the pathogenesis of iodide-induced autoimmune thyroiditis in NOD-H2 h4 mice. J Autoimmun. 29:195–202. 2007. View Article : Google Scholar : PubMed/NCBI
17	Armengol MP, Juan M, Lucas-Martín A, Fernández-Figueras MT, Jaraquemada D, Gallart T and Pujol-Borrell R: Thyroid autoimmune disease: Demonstration of thyroid antigen-specific B cells and recombination-activating gene expression in chemokine-containing active intrathyroidal germinal centers. Am J Pathol. 159:861–873. 2001. View Article : Google Scholar : PubMed/NCBI
18	Choi EW, Shin IS, Lee HW, Park SY, Park JH, Nam MH, Kim JS, Woo SK, Yoon EJ, Kang SK, et al: Transplantation of CTLA4Ig gene-transduced adipose tissue-derived mesenchymal stem cells reduces inflammatory immune response and improves Th1/Th2 balance in experimental autoimmune thyroiditis. J Gene Med. 13:3–16. 2011. View Article : Google Scholar : PubMed/NCBI
19	Kang SK, Shin IS, Ko MS, Jo JY and Ra JC: Journey of mesenchymal stem cells for homing: Strategies to enhance efficacy and safety of stem cell therapy. Stem Cells Int. 2012:3429682012. View Article : Google Scholar : PubMed/NCBI
20	Sakaguchi S, Ono M, Setoguchi R, Yagi H, Hori S, Fehervari Z, Shimizu J, Takahashi T and Nomura T: Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol rev. 212:8–27. 2006. View Article : Google Scholar : PubMed/NCBI
21	Wing K and Sakaguchi S: Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol. 11:7–13. 2010. View Article : Google Scholar : PubMed/NCBI
22	Yudoh K, Matsuno H, Nakazawa F, Yonezawa T and Kimura T: Reduced expression of the regulatory CD4+ T cell subset is related to Th1/Th2 balance and disease severity in rheumatoid arthritis. Arthritis Rheum. 43:617–627. 2000. View Article : Google Scholar : PubMed/NCBI
23	Arbabi S and Maier RV: Mitogen-activated protein kinases. Crit Care Med. 30 Suppl 1:S74–S79. 2002. View Article : Google Scholar
24	Schett G, Tohidast-Akrad M, Smolen JS, Schmid BJ, Steiner CW, Bitzan P, Zenz P, Redlich K, Xu Q and Steiner G: Activation, differential localization, and regulation of the stress-activated protein kinases, extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase, in synovial tissue and cells in rheumatoid arthritis. Arthritis Rheum. 43:2501–2512. 2000. View Article : Google Scholar : PubMed/NCBI
25	Zhao L, Liu X, Liang J, Han S, Wang Y, Yin Y, Luo Y and Li J: Phosphorylation of p38 MAPK mediates hypoxic preconditioning-induced neuroprotection against cerebral ischemic injury via mitochondria translocation of Bcl-xL in mice. Brain Res. 1503:78–88. 2013. View Article : Google Scholar : PubMed/NCBI
26	Johnson GL and Lapadat R: Mitogen-activated protein kinase pathways mediated by ERK, JNK and p38 protein kinases. Science. 298:1911–1912. 2002. View Article : Google Scholar : PubMed/NCBI
27	Ren G, Zhao X, Zhang L, Zhang J, L'Huillier A, Ling W, Roberts AI, Le AD, Shi S, Shao C and Shi Y: Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression. J immunol. 184:2321–2328. 2010. View Article : Google Scholar : PubMed/NCBI
28	Luz-Crawford P, Noël D, Fernandez X, Khoury M, Figueroa F, Carrión F, Jorgensen C and Djouad F: Mesenchymal stem cells repress Th17 molecular program through the PD-1 pathway. PLoS One. 7:e452722012. View Article : Google Scholar : PubMed/NCBI
29	Deng J, Zou ZM, Zhou TL, Su YP, Ai GP, Wang JP, Xu H and Dong SW: Bone marrow mesenchymal stem cells can be mobilized into peripheral blood by G-CSF in vivo and integrate into traumatically injured cerebral tissue. Neurolo Sci. 32:641–651. 2011. View Article : Google Scholar
30	Yen BL, Huang HI, Chien CC, Jui HY, Ko BS, Yao M, Shun CT, Yen ML, Lee MC and Chen YC: Isolation of multipotent cells from human term placenta. Stem Cells. 23:3–9. 2005. View Article : Google Scholar : PubMed/NCBI