Login Register Cart 0
Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Effect of Umbilical Cord Mesenchymal Stem Cell Transplantation Under LIFPUS Pretreatment on Thyroid Function in EAT Rats

Author(s): Ziyu Ren, Ronghua Fang, Wenzhen Deng, Jiangchuan Long and Dongfang Liu*

Volume 18, Issue 2, 2023

Published on: 02 August, 2022

Page: [260 - 275] Pages: 16

DOI: 10.2174/1574888X17666220513143100

Price: $65

conference banner
Abstract

Background: A growing number of studies have demonstrated that mesenchymal stem cells (MSCs) can effectively regulate the progression of multiple autoimmune diseases and can respond positively to mechanical stimulation by ultrasound in an in vitro setting to improve transplantation efficacy.

Objective: The aim of this study was to activate hUC-MSCs by pretreatment with low-intensity focused pulsed ultrasound (LIFPUS) in an in vitro environment and transplant them into a rat model of EAT via tail vein. To investigate the efficacy and potential mechanism of action of hUC-MSCs in the treatment of EAT.

Methods: In this study, 40 female lewis rats were divided into control, EAT, hUC-MSCs treatment and LIFPUS pretreatment transplantation group. EAT models were established by subcutaneous multi-point injection of PTG+Freund's adjuvant, and the primary hUC-MSCs were treated with different gradients of LIFPUS irradiation or sham irradiation in an in vitro environment and screened by Western Blot (WB), flow cytology cycle analysis, and cellular immunofluorescence to find the optimal treatment parameters for LIFPUS to promote cell proliferation. After tail vein injection of different pretreatment groups of hUC-MSCs, Homing sites of hUC-MSCs in vivo, circulating autoantibody expression levels and local thyroid histopathological changes were assessed by enzyme-linked immunosorbent assay (ELISA), spleen index, tissue hematoxylin-eosin (HE) staining and immunohistochemistry. The expression levels of apoptotic proteins Bcl-2, Bax and endoplasmic reticulum stress-related proteins Chop and EIF2α in thyroid tissue were also examined by WB.

Results: LIFPUS can effectively stimulate hUC-MSCs in vitro to achieve the most optimal proliferative and secretory activity. In the EAT model, hUC-MSCs can effectively reduce thyroid cell apoptosis, improve thyroid function and reduce excessive accumulation of autoimmune antibodies in the body. in comparison, the LIFPUS pretreatment group showed a more favorable treatment outcome. Further experiments demonstrated that hUC-MSCs transplantation may effectively inhibit the apoptotic state of thyroid follicles and follicular epithelial cells by down-regulating the unfolded protein reaction (UPR) of the PERK pathway, thus providing a therapeutic effect for AIT.

Conclusion: hUC-MSCs can effectively reverse the physiological function of EAT thyroid tissue and reduce the accumulation of circulating antibodies in the body. in comparison, hUC-MSCs under LIFPUS pretreatment showed more desirable therapeutic potential. hUC-MSCs transplanted under LIFPUS pretreatment may be a new class of safe therapeutic modality for the treatment of AIT.

Keywords: Mesenchymal stem cells, experimental autoimmune thyroiditis, low intensity focused pulsed ultrasound, cell cycle, apoptosis, thyroid function.

« Previous Next »
Graphical Abstract

[1]
Bianco P, Robey PG, Simmons PJ. Mesenchymal stem cells: Revisiting history, concepts, and assays. Cell Stem Cell 2008; 2(4): 313-9.
[http://dx.doi.org/10.1016/j.stem.2008.03.002] [PMID: 18397751]
[2]
Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): Role as guardians of inflammation. Mol Ther 2012; 20(1): 14-20.
[http://dx.doi.org/10.1038/mt.2011.211] [PMID: 22008910]
[3]
Herreros MD, Garcia-Arranz M, Guadalajara H, De-La-Quintana P, Garcia-Olmo D. Autologous expanded adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistulas: A phase III randomized clinical trial (FATT 1: Fistula Advanced Therapy Trial 1) and long-term evaluation. Dis Colon Rectum 2012; 55(7): 762-72.
[http://dx.doi.org/10.1097/DCR.0b013e318255364a] [PMID: 22706128]
[4]
Panés J, García-Olmo D, Van Assche G, et al. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex peria-nal fistulas in Crohn’s disease: A phase 3 randomised, double-blind controlled trial. Lancet 2016; 388(10051): 1281-90.
[http://dx.doi.org/10.1016/S0140-6736(16)31203-X] [PMID: 27477896]
[5]
Wang Y, Chen X, Cao W, Shi Y. Plasticity of mesenchymal stem cells in immunomodulation: Pathological and therapeutic implications. Nat Immunol 2014; 15(11): 1009-16.
[http://dx.doi.org/10.1038/ni.3002] [PMID: 25329189]
[6]
Sun L, Wang D, Liang J, et al. Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythemato-sus. Arthritis Rheum 2010; 62(8): 2467-75.
[http://dx.doi.org/10.1002/art.27548] [PMID: 20506343]
[7]
Dalal J, Gandy K, Domen J. Role of mesenchymal stem cell therapy in Crohn’s disease. Pediatr Res 2012; 71(4 Pt 2): 445-51.
[http://dx.doi.org/10.1038/pr.2011.56] [PMID: 22430380]
[8]
Ren G, Zhang L, Zhao X, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2008; 2(2): 141-50.
[http://dx.doi.org/10.1016/j.stem.2007.11.014] [PMID: 18371435]
[9]
Ullah M, Liu DD, Thakor AS. Mesenchymal stromal cell homing: Mechanisms and strategies for improvement. iScience 2019; 15: 421-38.
[http://dx.doi.org/10.1016/j.isci.2019.05.004] [PMID: 31121468]
[10]
De Becker A, Riet IV. Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy? World J Stem Cells 2016; 8(3): 73-87.
[http://dx.doi.org/10.4252/wjsc.v8.i3.73] [PMID: 27022438]
[11]
Liu DD, Ullah M, Concepcion W, Dahl JJ, Thakor AS. The role of ultrasound in enhancing mesenchymal stromal cell-based therapies. Stem Cells Transl Med 2020; 9(8): 850-66.
[http://dx.doi.org/10.1002/sctm.19-0391] [PMID: 32157802]
[12]
Costa V, Carina V, Fontana S, et al. Osteogenic commitment and differentiation of human mesenchymal stem cells by low-intensity pulsed ultrasound stimulation. J Cell Physiol 2018; 233(2): 1558-73.
[http://dx.doi.org/10.1002/jcp.26058] [PMID: 28621452]
[13]
Yamaguchi S, Aoyama T, Ito A, et al. Effect of low-intensity pulsed ultrasound after mesenchymal stromal cell injection to treat oste-ochondral defects: An in vivo study. Ultrasound Med Biol 2016; 42(12): 2903-13.
[http://dx.doi.org/10.1016/j.ultrasmedbio.2016.07.021] [PMID: 27600474]
[14]
Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: Clinical and diagnostic criteria. Autoimmun Rev 2014; 13(4-5): 391-7.
[http://dx.doi.org/10.1016/j.autrev.2014.01.007] [PMID: 24434360]
[15]
Lazúrová I, Benhatchi K. Autoimmune thyroid diseases and nonorgan specific autoimmunity. Pol Arch Med Wewn 2012; 122 (Suppl. 1): 55-9.
[PMID: 23222800]
[16]
Twig G, Shina A, Amital H, Shoenfeld Y. Pathogenesis of infertility and recurrent pregnancy loss in thyroid autoimmunity. J Autoimmun 2012; 38(2-3): J275-81.
[http://dx.doi.org/10.1016/j.jaut.2011.11.014] [PMID: 22218218]
[17]
Thangaratinam S, Tan A, Knox E, Kilby MD, Franklyn J, Coomarasamy A. Association between thyroid autoantibodies and miscarriage and preterm birth: Meta-analysis of evidence. BMJ 2011; 342(may09 1): d2616.
[http://dx.doi.org/10.1136/bmj.d2616] [PMID: 21558126]
[18]
Fei X, Jiang S, Zhang S, et al. Isolation, culture, and identification of amniotic fluid-derived mesenchymal stem cells. Cell Biochem Biophys 2013; 67(2): 689-94.
[http://dx.doi.org/10.1007/s12013-013-9558-z] [PMID: 23508888]
[19]
Hou Y, Guo X, Zhang C, et al. Protective effects of Jiayan Kangtai granules on autoimmune thyroiditis in a rat model by modulating Th17/Treg cell balance. J Tradit Chin Med 2018; 38(3): 380-90.
[http://dx.doi.org/10.1016/S0254-6272(18)30628-9] [PMID: 32185970]
[20]
Beane OS, Darling EM. Isolation, characterization, and differentiation of stem cells for cartilage regeneration. Ann Biomed Eng 2012; 40(10): 2079-97.
[http://dx.doi.org/10.1007/s10439-012-0639-8] [PMID: 22907257]
[21]
Salgado AJ, Oliveira JM, Martins A, et al. Tissue engineering and regenerative medicine: Past, present, and future. Int Rev Neurobiol 2013; 108: 1-33.
[http://dx.doi.org/10.1016/B978-0-12-410499-0.00001-0] [PMID: 24083429]
[22]
Gao F, Chiu SM, Motan DA, et al. Mesenchymal stem cells and immunomodulation: Current status and future prospects. Cell Death Dis 2016; 7(1): e2062.
[http://dx.doi.org/10.1038/cddis.2015.327] [PMID: 26794657]
[23]
Han Y, Li X, Zhang Y, Han Y, Chang F, Ding J. Mesenchymal stem cells for regenerative medicine. Cells 2019; 8(8): 886.
[http://dx.doi.org/10.3390/cells8080886] [PMID: 31412678]
[24]
De Miguel MP, Fuentes-Julián S, Blázquez-Martínez A, et al. Immunosuppressive properties of mesenchymal stem cells: Advances and applications. Curr Mol Med 2012; 12(5): 574-91.
[http://dx.doi.org/10.2174/156652412800619950] [PMID: 22515979]
[25]
Devine SM, Cobbs C, Jennings M, Bartholomew A, Hoffman R. Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood 2003; 101(8): 2999-3001.
[http://dx.doi.org/10.1182/blood-2002-06-1830] [PMID: 12480709]
[26]
Nitzsche F, Müller C, Lukomska B, Jolkkonen J, Deten A, Boltze J. Concise review: MSC adhesion cascade-insights into homing and transendothelial migration. Stem Cells 2017; 35(6): 1446-60.
[http://dx.doi.org/10.1002/stem.2614] [PMID: 28316123]
[27]
Hu C, Wu Z, Li L. Pre-treatments enhance the therapeutic effects of mesenchymal stem cells in liver diseases. J Cell Mol Med 2020; 24(1): 40-9.
[http://dx.doi.org/10.1111/jcmm.14788] [PMID: 31691463]
[28]
Burks SR, Ziadloo A, Kim SJ, Nguyen BA, Frank JA. Noninvasive pulsed focused ultrasound allows spatiotemporal control of targeted homing for multiple stem cell types in murine skeletal muscle and the magnitude of cell homing can be increased through repeated applications. Stem Cells 2013; 31(11): 2551-60.
[http://dx.doi.org/10.1002/stem.1495] [PMID: 23922277]
[29]
Swirski FK, Nahrendorf M, Etzrodt M, et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 2009; 325(5940): 612-6.
[http://dx.doi.org/10.1126/science.1175202] [PMID: 19644120]
[30]
Ling L, Feng X, Wei T, et al. Effects of low-intensity pulsed ultrasound (LIPUS)-pretreated human amnion-derived mesenchymal stem cell (hAD-MSC) transplantation on primary ovarian insufficiency in rats. Stem Cell Res Ther 2017; 8(1): 283.
[http://dx.doi.org/10.1186/s13287-017-0739-3] [PMID: 29258619]
[31]
Zheng J, Li H, He L, et al. Preconditioning of umbilical cord-derived mesenchymal stem cells by rapamycin increases cell migration and ameliorates liver ischaemia/reperfusion injury in mice via the CXCR4/CXCL12 axis. Cell Prolif 2019; 52(2): e12546.
[http://dx.doi.org/10.1111/cpr.12546] [PMID: 30537044]
[32]
Xu K, Lee JY, Kaneko Y, et al. Human stem cells transplanted into the rat stroke brain migrate to the spleen via lymphatic and inflammation pathways. Haematologica 2019; 104(5): 1062-73.
[http://dx.doi.org/10.3324/haematol.2018.206581] [PMID: 30514806]
[33]
Aoshi T, Zinselmeyer BH, Konjufca V, et al. Bacterial entry to the splenic white pulp initiates antigen presentation to CD8+ T cells. Immunity 2008; 29(3): 476-86.
[http://dx.doi.org/10.1016/j.immuni.2008.06.013] [PMID: 18760639]
[34]
Mebius RE, Kraal G. Structure and function of the spleen. Nat Rev Immunol 2005; 5(8): 606-16.
[http://dx.doi.org/10.1038/nri1669] [PMID: 16056254]

Rights & Permissions Print Cite
Article Metrics
4
© 2024 Bentham Science Publishers | Privacy Policy