Bone marrow mesenchymal stem cells transplantation attenuates type 1 diabetes mellitus by immune suppressing T cells

YU Jia-shan, YANG Wen-jiang, PENG Li-juan, GAO Jie, LI Hong, SU Min, HU Rong

Chinese Journal of Clinical Anatomy ›› 2020, Vol. 38 ›› Issue (6) : 668-673.

Chinese Journal of Clinical Anatomy ›› 2020, Vol. 38 ›› Issue (6) : 668-673. DOI: 10.13418/j.issn.1001-165x.2020.06.009

Bone marrow mesenchymal stem cells transplantation attenuates type 1 diabetes mellitus by immune suppressing T cells

  • YU Jia-shan, YANG Wen-jiang, PENG Li-juan, GAO Jie, LI Hong, SU Min, HU Rong
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Abstract

Objective To investigate the effects and mechanism of bone marrow mesenchymal stem cells (BMSCs) transplantation on Type 1 diabetes mellitus (T1DM) mice. Methods Isolation, culture and identification of BMSCs were performed. BMSCs supernatant was used to be the conditioned medium after third passage (P3), co-cultured with 2 weeks NOD splenocytes, and the proliferation and activation of CD4+ and CD8+T cells were detected by FACS. Two weeks female NOD mice were randomly divided into three groups: a BMSCs group, a PBS group and a control group (6 mice in each group). Mice in the control group were killed at 2 weeks. 100 μl (2×107 cells) BMSCs or equal volume PBS was injected intraperitoneally at 12 weeks in the BMSCs group and the PBS group respectively, then the mice were monitored for blood glucose and body weight till 26 weeks. Inflammatory cells infiltration of pancreases was detected by H&E, immunohistochemical and immunofluorescent staining. The splenocytes were extracted to observe the proliferation and activation of CD4+ and CD8+T cells by FACS. Results BMSCs were successfully isolated and cultured. BMSCs conditioned medium inhibited the proliferation and activation of CD4+ and CD8+T cells (P<0.05). Mice body weight of BMSCs group was higher than that of PBS group (P<0.05), the incidence rate of diabetes and inflammatory infiltration decreased (P<0.05) as well as the proliferation and activation of CD4+ and CD8+ T cells in the spleen (P<0.05). Conclusions BMSCs transplantation may attenuate T1DM by immune suppressing T cells.

Key words

BMSCs /  NOD/ShiLtJ mice /  T1DM Immunosuppression /  T cells

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YU Jia-shan, YANG Wen-jiang, PENG Li-juan, GAO Jie, LI Hong, SU Min, HU Rong. Bone marrow mesenchymal stem cells transplantation attenuates type 1 diabetes mellitus by immune suppressing T cells[J]. Chinese Journal of Clinical Anatomy. 2020, 38(6): 668-673 https://doi.org/10.13418/j.issn.1001-165x.2020.06.009

References

[1]  Medina A, Parween S, Ullsten S, et al. Early deficits in insulin secretion, beta cell mass and islet blood perfusion precede onset of autoimmune type 1 diabetes in BioBreeding rats[J]. Diabetologia, 2018, 61(4):896-905.
[2] Sims EK, Dimeglio LA. Cause or effect? A review of clinical data demonstrating beta cell dysfunction prior to the clinical onset of type 1 diabetes[J]. Molecular Metabolism, 2019, 27(suppl): S129-S138.
[3] Xv J, Ming Q, Wang X, et al. Mesenchymal stem cells moderate immune response of type 1 diabetes[J]. Cell Tissue Res, 2017, 368(2): 239-248.
[4] Gülden E, Palm N, Herold KC. MAIT Cells: A Link between Gut Integrity and Type 1 Diabetes[J]. Cell Metabolism, 2017, 26(6): 813-815.
[5] Boháčová P, Holáň V. Mesenchymal stem cells and type 1 diabetes treatment[J]. Vnitrni Lekarstvi, 2018, 64(7-8): 725-728.
[6] Liang C, Jiang E, Yao J, et al. Interferon-γ mediates the immunosuppression of bone marrow mesenchymal stem cells on T-lymphocytes in vitro[J]. Hematology, 2018, 23(1): 44-49.
[7] Andrew SN, Massimo M, Jeffrey RA, et al. Oral therapy with colonization factor antigen I prevents development of type 1 diabetes in Non-obese Diabetic mice[J]. Scientific Reports, 2020, 10(1): 1-15.
[8] Tian X, Lin Y, Cui C, et al. BTNL2-Ig Protein Attenuates Type 1 Diabetes in Non-Obese Diabetic (NOD) Mice[J]. Advanced healthcare materials, 2019, 8(9): 1-7.
[9] Jamal MA, Bahare N, Shima R, et al. Immunomodulatory and protective effects of adipose tissue-derived mesenchymal stem cells in an allograft islet composite transplantation for experimental autoimmune type 1 diabetes[J]. Immunol Lett, 2017, 188(17): 21-31.
[10]廖文萍, 胡蓉, 黄悦, 等. 骨髓间充质干细胞异体移植对小鼠实验性自身免疫性脑脊髓炎的治疗作用[J]. 解剖学报, 2017, 48(3): 266-272.
[11]Zhang W, Zhou L, Dang J, et al. Human gingiva-derived mesenchymal stem cells ameliorate streptozoticin-induced T1DM in mice via suppression of T effector cells and up-regulating treg subsets[J]. Sci Rep, 2017, 7(1): 1-12.
[12]Relation T, Yi T, Guess AJ, et al. Intratumoral delivery of interferonc-secreting mesenchymal stromal cells repolarizes Tumor-associated macrophages and suppresses neuroblastoma proliferation in vivo[J]. Stem Cells, 2018, 36(6): 915-924.
[13]Lee HJ, Kim SN, Jeon MS, et al. ICOSL expression in human bone marrow-derived mesenchymal stem cells promotes induction of regulatory T cells[J]. Sci Rep, 2017, 7(7): 1-15.
[14]Wu X, Wang Y, Xu J, et al. MM-BMSCs induce naïve CD4+ T lymphocytes dysfunction through fibroblast activation protein α[J]. Oncotarget, 2017, 8(32): 52614-52628.
[15] Reddy S, Zeng N, Al-Diery H, et al. Analysis of peri-islet CD45-positive leucocytic infiltrates in long-standing type 1 diabetic patients: additional data regarding cause of death[J]. Diabetologia, 2015, 58(8): 1959-1959.

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