Human Gingiva Tissue-derived MSC Ameliorates Immune-mediated Bone Marrow Failure of Aplastic Anemia Suppression of Th1 and Th17 Cells and Enhancement of CD4+Foxp3+ Regulatory T Cells Differentiation

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2020 Jan 15

PMID 31934306

Citations 27

Authors

Jianzhi Zhao

Jingrong Chen

Feng Huang

Julie Wang

Wenru Su

Jianyao Zhou

Quanyin Qi

Fenglin Cao

Baoqing Sun

Zhongmin Liu

Joseph A Bellanti

Songguo Zheng

Affiliations

Soon will be listed here.

Abstract

Accumulating evidence has revealed that human gingiva-derived mesenchymal stem cells (GMSCs) are emerging as a new line of mesenchymal stem cells and may have the potential to control or even treat autoimmune diseases through maintaining the balance between Th and Treg cells. Given that GMSCs have a robust immune regulatory function and regenerative ability, we investigated the effect of GMSCs on preventing T cell-mediated bone marrow failure (BMF) in a mouse model. We observed that GMSCs markedly improved mice survival and attenuated histological bone marrow (BM) damage. Moreover, we found GMSCs significantly reduced cell infiltration of CD8+ cells, Th1 and Th17 cells, whereas increased CD4+Foxp3+ regulatory T cells (Tregs) differentiation in lymph nodes. GMSCs also suppressed the levels of TNF-α, IFN-γ, IL-17A and IL-6, but IL-10 was increased in serum. The live imaging identified that GMSCs can home into inflammatory location on BM. Our results demonstrate that GMSCs attenuate T cell-mediated BMF through regulating the balance of Th1, Th17 and Tregs, implicating that application of GMSCs may provide a promising approach in prevention and treatment of patients with aplastic anemia.

Citing Articles

Mesenchymal Stem/Stromal Cells Derived from Dental Tissues Mediate the Immunoregulation of T Cells through the Purinergic Pathway.

Poblano-Perez L, Monroy-Garcia A, Fragoso-Gonzalez G, Mora-Garcia M, Castell-Rodriguez A, Mayani H Int J Mol Sci. 2024; 25(17).

PMID: 39273524 PMC: 11395442. DOI: 10.3390/ijms25179578.

Gingival mesenchymal stem cells: Biological properties and therapeutic applications.

Peng Y, Jaar J, Tran S J Oral Biol Craniofac Res. 2024; 14(5):547-569.

PMID: 39108352 PMC: 11301388. DOI: 10.1016/j.jobcr.2024.07.003.

Gingival-derived mesenchymal stem cells alleviate allergic asthma inflammation via HGF in animal models.

Fang Q, Wu W, Xiao Z, Zeng D, Liang R, Wang J iScience. 2024; 27(5):109818.

PMID: 38766356 PMC: 11099335. DOI: 10.1016/j.isci.2024.109818.

miRNA-148a-containing GMSC-derived EVs modulate Treg/Th17 balance via IKKB/NF-κB pathway and treat a rheumatoid arthritis model.

Chen J, Shi X, Deng Y, Dang J, Liu Y, Zhao J JCI Insight. 2024; 9(10).

PMID: 38652539 PMC: 11141912. DOI: 10.1172/jci.insight.177841.

Mesenchymal Stem Cell Transplantation in Type 1 Diabetes Treatment: Current Advances and Future Opportunity.

Liu J, Wan X, Zheng S, Khan M, He H, Feng Y Curr Stem Cell Res Ther. 2023; 19(9):1175-1184.

PMID: 37817652 DOI: 10.2174/011574888X268740231002054459.

References

Huang F, Liu Z, Zheng S . Updates on GMSCs Treatment for Autoimmune Diseases. Curr Stem Cell Res Ther. 2018; 13(5):345-349. DOI: 10.2174/1574888X13666180220141114. View

Zeng W, Kajigaya S, Chen G, Risitano A, Nunez O, Young N . Transcript profile of CD4+ and CD8+ T cells from the bone marrow of acquired aplastic anemia patients. Exp Hematol. 2004; 32(9):806-14. DOI: 10.1016/j.exphem.2004.06.004. View

Park M, Park C, Cho Y, Jang S, Lee J, Lee J . Alterations in the bone marrow microenvironment may elicit defective hematopoiesis: a comparison of aplastic anemia, chronic myeloid leukemia, and normal bone marrow. Exp Hematol. 2016; 45:56-63. DOI: 10.1016/j.exphem.2016.09.009. View

Luo Y, Zheng S . Hall of Fame among Pro-inflammatory Cytokines: Interleukin-6 Gene and Its Transcriptional Regulation Mechanisms. Front Immunol. 2017; 7:604. PMC: 5165036. DOI: 10.3389/fimmu.2016.00604. View

Ma J, Yu J, Tao X, Cai L, Wang J, Zheng S . The imbalance between regulatory and IL-17-secreting CD4+ T cells in lupus patients. Clin Rheumatol. 2010; 29(11):1251-8. DOI: 10.1007/s10067-010-1510-7. View

Kordasti S, Afzali B, Lim Z, Ingram W, Hayden J, Barber L . IL-17-producing CD4(+) T cells, pro-inflammatory cytokines and apoptosis are increased in low risk myelodysplastic syndrome. Br J Haematol. 2009; 145(1):64-72. DOI: 10.1111/j.1365-2141.2009.07593.x. View

Li N, Wang J, Liang T, Zhu M, Wang J, Fu X . Pathologic finding of increased expression of interleukin-17 in the synovial tissue of rheumatoid arthritis patients. Int J Clin Exp Pathol. 2013; 6(7):1375-9. PMC: 3693203. View

Young N, Scheinberg P, Calado R . Aplastic anemia. Curr Opin Hematol. 2008; 15(3):162-8. PMC: 3410534. DOI: 10.1097/MOH.0b013e3282fa7470. View

Yan L, Fu R, Liu H, Wang H, Liu C, Wang T . Abnormal quantity and function of regulatory T cells in peripheral blood of patients with severe aplastic anemia. Cell Immunol. 2015; 296(2):95-105. DOI: 10.1016/j.cellimm.2015.04.001. View

10.

Zhao J, Wang J, Dang J, Zhu W, Chen Y, Zhang X . A preclinical study-systemic evaluation of safety on mesenchymal stem cells derived from human gingiva tissue. Stem Cell Res Ther. 2019; 10(1):165. PMC: 6567625. DOI: 10.1186/s13287-019-1262-5. View

11.

Solomou E, Rezvani K, Mielke S, Malide D, Keyvanfar K, Visconte V . Deficient CD4+ CD25+ FOXP3+ T regulatory cells in acquired aplastic anemia. Blood. 2007; 110(5):1603-6. PMC: 1975843. DOI: 10.1182/blood-2007-01-066258. View

12.

Pan H, Leng R, Li X, Zheng S, Ye D . Targeting T-helper 9 cells and interleukin-9 in autoimmune diseases. Cytokine Growth Factor Rev. 2014; 24(6):515-22. DOI: 10.1016/j.cytogfr.2013.09.001. View

13.

Hinterberger W, Rowlings P, Gibson J, Jacobsen N, Klein J, Kolb H . Results of transplanting bone marrow from genetically identical twins into patients with aplastic anemia. Ann Intern Med. 1997; 126(2):116-22. DOI: 10.7326/0003-4819-126-2-199701150-00004. View

14.

Cassano J, Schnabel L, Goodale M, Fortier L . The immunomodulatory function of equine MSCs is enhanced by priming through an inflammatory microenvironment or TLR3 ligand. Vet Immunol Immunopathol. 2017; 195:33-39. DOI: 10.1016/j.vetimm.2017.10.003. View

15.

Le Blanc K, Ringden O . Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med. 2007; 262(5):509-25. DOI: 10.1111/j.1365-2796.2007.01844.x. View

16.

Le Blanc K, Samuelsson H, Gustafsson B, Remberger M, Sundberg B, Arvidson J . Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia. 2007; 21(8):1733-8. DOI: 10.1038/sj.leu.2404777. View

17.

Yang S, Wang J, Brand D, Zheng S . Role of TNF-TNF Receptor 2 Signal in Regulatory T Cells and Its Therapeutic Implications. Front Immunol. 2018; 9:784. PMC: 5916970. DOI: 10.3389/fimmu.2018.00784. View

18.

Broglie L, Margolis D, Medin J . Yin and Yang of mesenchymal stem cells and aplastic anemia. World J Stem Cells. 2018; 9(12):219-226. PMC: 5746642. DOI: 10.4252/wjsc.v9.i12.219. View

19.

Cruz M, Dissaranan C, Cotleur A, Kiedrowski M, Penn M, Damaser M . Pelvic organ distribution of mesenchymal stem cells injected intravenously after simulated childbirth injury in female rats. Obstet Gynecol Int. 2011; 2012:612946. PMC: 3177359. DOI: 10.1155/2012/612946. View

20.

Gu J, Ni X, Pan X, Lu H, Lu Y, Zhao J . Human CD39 regulatory T cells present stronger stability and function under inflammatory conditions. Cell Mol Immunol. 2016; 14(6):521-528. PMC: 5518817. DOI: 10.1038/cmi.2016.30. View