Transplantation of human stem cells from the apical papilla
for treating dextran sulfate sodium-induced experimental colitis

doi:10.3969/j.issn.2095-4344.2010

Abstract

Abstract:

BACKGROUND: Stem cells from the apical papilla (SCAP) play important roles in the formation and development of dental roots. However, the immune-modulating capacity of SCAP has not been fully elucidated.

OBJECTIVE: To test the therapeutic effects of transplantation of SCAP on dextran sulfate sodium-induced experimental colitis.

METHODS: Twenty-four C57/BL6 mice were equally divided into four groups (normal control, positive control, SCAP treatment group, and FasL-knockdown SCAP group), and latter three groups of mice were induced to acute experimental colitis by 3% dextran sulfate sodium in drinking water. At day 3 after modeling, model mice were treated with PBS, human SCAP (2×10⁶ cells), and FasL-knockdown SCAP via intraperitoneal injection, respectively. Inflammation was evaluated by measuring body mass and length of the colon, detecting levels of interleukin 1β, interleukin 6 and tumor necrosis factor α, as well as histological analyses at day 10 after modeling. Levels of Tregs in mesenteric lymph nodes in mice were detected using flow cytometric analysis.

RESULTS AND CONCLUSION: SCAP transplantation could ameliorate the inflammation in dextran sulfate sodium-induced colitis mice, and body mass loss and symptoms were significantly improved. Pathological score and the levels of three inflammatory cytokines in the colon tissue decreased significantly. Flow cytometric analysis revealed an increased level of Tregs in mesenteric lymph nodes. Knocking down of FasL gene in SCAP abrogated the therapeutic effects of SCAP in ameliorating dextran sulphate sodium-induced colitis. Therefore, Fas-FasL pathway played an important role in the underlying mechanism of the immune-modulating capacity of SCAP.

Key words: experimental colitis, dextran sulfate sodium, stem cells from the apical papilla, immunomodulation, inflammatory factor, Fas-FasL pathway

CLC Number:

Li Jia, Tang Ying, Zhu Qi, Zhang Yanping, Zhou Peigang, Gu Yongchun. Transplantation of human stem cells from the apical papilla for treating dextran sulfate sodium-induced experimental colitis [J]. Chinese Journal of Tissue Engineering Research, 2020, 24(7): 1069-1075.

Figures/Tables 6

References

[1] WIRTZ S, NEUFERT C, WEIGMANN B, et al. Chemically induced mouse models of intestinal inflammation. Nat Protoc. 2007;2(3): 541-546.
[2] ABRAHAM C, CHO JH. Inflammatory bowel disease. N Engl J Med. 2009;361(21):2066-2078.
[3] BAUMGART DC, SANDBORN WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007; 369 (9573):1641-1657.
[4] BERNSTEIN CN. Treatment of IBD: where we are and where we are going. Am J Gastroenterol. 2015;110(1):114-126.
[5] 王伟强. IL-37b基因修饰的骨髓间充质干细胞对DSS诱导的肠炎缓解作用的研究[D]. 天津:天津医科大学,2015.
[6] ALGERI M, CONFORTI A, PITISCI A, et al. Mesenchymal stromal cells and chronic inflammatory bowel disease. Immunol Lett. 2015; 168(2): 191-200.
[7] SHI M, LIU ZW, WANG FS. Immunomodulatory properties and therapeutic application of mesenchymal stem cells. Clin Exp Immunol. 2011;164(1):1-8.
[8] YI T, SONG SU. Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications. Arch Pharm Res. 2012;35(2): 213-221.
[9] YE L, WU XW, YU N, et al. Clinical efficacy and safety of stem cells in refractory Crohn"s disease: A systematic review. J Cell Immunother. 2016;2(1): 21-27.
[10] LIU Y, WANG L, LIU S, et al. Transplantation of SHED prevents bone loss in the early phase of ovariectomy-induced osteoporosis. J Dent Res. 2014;93(11):1124-1132.
[11] XU X, CHEN C, AKIYAMA K, et al. Gingivae contain neural-crest- and mesoderm-derived mesenchymal stem cells. J Dent Res. 2013;92(9): 825-832.
[12] YAMAZA T, KENTARO A, CHEN C, et al. Immunomodulatory properties of stem cells from human exfoliated deciduous teeth. Stem Cell Res Ther. 2010;1(1):5.
[13] DE LA PORTILLA F, ALBA F, GARCÍA-OLMO D, et al. Expanded allogeneic adipose-derived stem cells (eASCs) for the treatment of complex perianal fistula in Crohn's disease: results from a multicenter phase I/IIa clinical trial. Int J Colorectal Dis. 2013;28(3):313-323.
[14] SONOYAMA W, LIU Y, YAMAZA T, et al. Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. J Endod. 2008;34(2):166-171.
[15] CHUNG CY, PARK YL, KIM N, et al. Rice prolamin extract ameliorates acute murine colitis by inhibiting nuclear factor-kappa B and modulating intestinal apoptosis and cell proliferation. Clin Exp Immunol. 2014;178(3): 537-547.
[16] SANN H, ERICHSEN JV, HESSMANN M, et al. Efficacy of drugs used in the treatment of IBD and combinations thereof in acute DSS-induced colitis in mice. Life Sci. 2013;92(12):708-718.
[17] COOPER HS, MURTHY SN, SHAH RS, et al. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993; 69(2):238-249.
[18] PODOLSKY DK,夏冰,陈志涛.炎症性肠病的发病机制[J].中华消化杂志, 2008,28(12):797-799.
[19] CHEN C, AKIYAMA K, YAMAZA T, et al. Telomerase governs immunomodulatory properties of mesenchymal stem cells by regulating FAS ligand expression. EMBO Mol Med. 2014;6(3):322-334.
[20] 赵璐,于莉,袁萍,等.根尖乳头干细胞与牙周膜干细胞的生物学行为比较[J].中国组织工程研究, 2016, 20(1):113-117.
[21] BAKOPOULOU A, LEYHAUSEN G, VOLK J, et al. Comparative analysis of in vitro osteo/odontogenic differentiation potential of human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAP). Arch Oral Biol. 2011;56(7):709-721.
[22] HUANG GT, SONOYAMA W, LIU Y, et al. The hidden treasure in apical papilla: the potential role in pulp/dentin regeneration and bioroot engineering. J Endod. 2008;34(6):645-651.
[23] DING G, LIU Y, AN Y, et al. Suppression of T cell proliferation by root apical papilla stem cells in vitro. Cells Tissues Organs. 2010;191(5): 357-364.
[24] ZHANG Q, SHI S, LIU Y, et al. Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis. J Immunol. 2009;183(12):7787-7798.
[25] GONZÁLEZ MA, GONZALEZ-REY E, RICO L, et al. Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology. 2009; 136(3):978-989.
[26] HERREROS MD, GARCIA-ARRANZ M, GUADALAJARA H, et al. 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):762-772.
[27] FÖLDES A, KÁDÁR K, KERÉMI B, et al. Mesenchymal Stem Cells of Dental Origin-Their Potential for Antiinflammatory and Regenerative Actions in Brain and Gut Damage. Curr Neuropharmacol. 2016;14(8): 914-934.
[28] 黄毅,周国华.辅助性CD4~+T细胞及其亚群与炎症性肠病关系的研究进展[J].临床消化病杂志,2016,28(3):196-198.
[29] 陈丹,朱若凯.辅助性T细胞及相关细胞因子与炎症性肠病的关系[J].实验与检验医学,2018,36(5):8-11.
[30] AKIYAMA K, CHEN C, WANG D, et al. Mesenchymal-stem-cell- induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell. 2012;10(5):544-555.