Differentiation of Pancreatic Beta Cells: Dual Acting of Inflammatory Factors


Cite item

Full Text

Abstract

In the past decades, scientists have made outstanding efforts to treat diabetes. However, diabetes treatment is still far from satisfactory due to the complex nature of the disease and the challenges encountered in resolving it. Inflammatory factors are key regulators of the immune system's response to pathological insults, organ neogenesis, rejuvenation of novel cells to replace injured cells and overwhelming disease conditions. Currently, the available treatments for type 1 diabetes include daily insulin injection, pancreatic beta cell or tissue transplantation, and gene therapy. Cell therapy, exploiting differentiation, and reprogramming various types of cells to generate pancreatic insulin-producing cells are novel approaches for the treatment of type 1 diabetes. A better understanding of the inflammatory pathways offers valuable and improved therapeutic options to provide more advanced and better treatments for diabetes. In this review, we investigated different types of inflammatory factors that participate in the pathogenesis of type 1 diabetes, their possible dual impacts on the differentiation, reprogramming, and fusion of other stem cell lines into pancreatic insulin-producing beta cells, and the possibility of applying these factors to improve the treatment of this disease.

About the authors

Faeze Shahedi

Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences

Email: info@benthamscience.net

Arron Munggela Foma

Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences

Email: info@benthamscience.net

Azam Mahmoudi-Aznaveh

Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences

Email: info@benthamscience.net

Mohammad Ali Mazlomi

Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences

Email: info@benthamscience.net

Zahra Azizi

Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

Mohammad Reza Khorramizadeh

Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

References

  1. Rotondi M, Chiovato L, Romagnani S, Serio M, Romagnani P. Role of chemokines in endocrine autoimmune diseases. Endocr Rev 2007; 28(5): 492-520. doi: 10.1210/er.2006-0044 PMID: 17475924
  2. Turley S, Poirot L, Hattori M, Benoist C, Mathis D. Physiological beta cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model. J Exp Med 2003; 198(10): 1527-37. doi: 10.1084/jem.20030966 PMID: 14623908
  3. Tanaka S, Nishida Y, Aida K, et al. Enterovirus infection, CXC chemokine ligand 10 (CXCL10), and CXCR3 circuit: A mechanism of accelerated beta-cell failure in fulminant type 1 diabetes. Diabetes 2009; 58(10): 2285-91. doi: 10.2337/db09-0091 PMID: 19641142
  4. Sarkar SA, Lee CE, Victorino F, et al. Expression and regulation of chemokines in murine and human type 1 diabetes. Diabetes 2012; 61(2): 436-46. doi: 10.2337/db11-0853 PMID: 22210319
  5. Ardestani A, Maedler K. The hippo signaling pathway in pancreatic β-cells: Functions and regulations. Endocr Rev 2018; 39(1): 21-35. doi: 10.1210/er.2017-00167 PMID: 29053790
  6. Geravandi S, Mahmoudi-aznaveh A, Azizi Z, Maedler K, Ardestani A. SARS-CoV-2 and pancreas: A potential pathological interaction? Trends Endocrinol Metab 2021; 32(11): 842-5. doi: 10.1016/j.tem.2021.07.004 PMID: 34373155
  7. Gagnerault MC, Luan JJ, Lotton C, Lepault F. Pancreatic lymph nodes are required for priming of beta cell reactive T cells in NOD mice. J Exp Med 2002; 196(3): 369-77. doi: 10.1084/jem.20011353 PMID: 12163565
  8. Spears E, Serafimidis I, Powers AC, Gavalas A. Debates in pancreatic beta cell biology: Proliferation versus progenitor differentiation and transdifferentiation in restoring β cell mass. Front Endocrinol 2021; 12: 722250. doi: 10.3389/fendo.2021.722250 PMID: 34421829
  9. Rhode A, Pauza ME, Barral AM, Rodrigo E, Oldstone MB, von Herrath MG, et al. Islet-specific expression of CXCL10 causes spontaneous islet infiltration and accelerates diabetes development. J Immunol 2005; 175(6): 3516-24. doi: 10.4049/jimmunol.175.6.3516
  10. Mallone R, Brezar V, Boitard C. T cell recognition of autoantigens in human type 1 diabetes: clinical perspectives. Clin Dev Immunol 2011; 2011: 513210. doi: 10.1155/2011/513210 PMID: 21785617
  11. Roep BO, Kracht MJL, van Lummel M, Zaldumbide A. A roadmap of the generation of neoantigens as targets of the immune system in type 1 diabetes. Curr Opin Immunol 2016; 43: 67-73. doi: 10.1016/j.coi.2016.09.007 PMID: 27723537
  12. McLaughlin RJ, de Haan A, Zaldumbide A, et al. Human islets and dendritic cells generate post-translationally modified islet autoantigens. Clin Exp Immunol 2016; 185(2): 133-40. doi: 10.1111/cei.12775 PMID: 26861694
  13. Eizirik DL, Sammeth M, Bouckenooghe T, et al. The human pancreatic islet transcriptome: Expression of candidate genes for type 1 diabetes and the impact of pro-inflammatory cytokines. PLoS Genet 2012; 8(3): e1002552. doi: 10.1371/journal.pgen.1002552 PMID: 22412385
  14. Costes S, Bertrand G, Ravier MA. Mechanisms of beta-cell apoptosis in type 2 diabetes-prone situations and potential protection by GLP-1-based therapies. Int J Mol Sci 2021; 22(10): 5303. doi: 10.3390/ijms22105303 PMID: 34069914
  15. Knip M, Siljander H. The role of the intestinal microbiota in type 1 diabetes mellitus. Nat Rev Endocrinol 2016; 12(3): 154-67. doi: 10.1038/nrendo.2015.218 PMID: 26729037
  16. Kostic AD, Gevers D, Siljander H, et al. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe 2015; 17(2): 260-73. doi: 10.1016/j.chom.2015.01.001 PMID: 25662751
  17. Zhang X, Zhivaki D, Lo-Man R. Unique aspects of the perinatal immune system. Nat Rev Immunol 2017; 17(8): 495-507. doi: 10.1038/nri.2017.54 PMID: 28627520
  18. Kawabe T, Jankovic D, Kawabe S, et al. Memory-phenotype CD4 + T cells spontaneously generated under steady-state conditions exert innate TH 1-like effector function. Sci Immunol 2017; 2(12): eaam9304. doi: 10.1126/sciimmunol.aam9304 PMID: 28783663
  19. Kieper WC, Troy A, Burghardt JT, Ramsey C, Lee JY, Jiang HQ, et al. Recent immune status determines the source of antigens that drive homeostatic T cell expansion. Journal of immunology 2005; 174(6): 3158-63. doi: 10.4049/jimmunol.174.6.3158
  20. Jameson SC, Lee YJ, Hogquist KA. Innate memory T cells. Adv Immunol 2015; 126: 173-213. doi: 10.1016/bs.ai.2014.12.001 PMID: 25727290
  21. Christianson SW, Shultz LD, Leiter EH. Adoptive transfer of diabetes into immunodeficient NOD-scid/scid mice. Relative contributions of CD4+ and CD8+ T-cells from diabetic versus prediabetic NOD.NON-Thy-1a donors. Diabetes 1993; 42(1): 44-55. doi: 10.2337/diab.42.1.44 PMID: 8093606
  22. Wen L, Ley RE, Volchkov PY, et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 2008; 455(7216): 1109-13. doi: 10.1038/nature07336 PMID: 18806780
  23. Yang W, Cong Y. Gut microbiota-derived metabolites in the regulation of host immune responses and immune-related inflammatory diseases. Cell Mol Immunol 2021; 18(4): 866-77. doi: 10.1038/s41423-021-00661-4 PMID: 33707689
  24. Wu W, Syed F, Simpson E, et al. Impact of proinflammatory cytokines on alternative splicing patterns in human islets. Diabetes 2022; 71(1): 116-27. doi: 10.2337/db20-0847
  25. Pan G, Mu Y, Hou L, Liu J. Examining the therapeutic potential of various stem cell sources for differentiation into insulin-producing cells to treat diabetes. Ann Endocrinol 2019; 80(1): 47-53. doi: 10.1016/j.ando.2018.06.1084 PMID: 30041820
  26. Azizi Z, Lange C, Paroni F, et al. β-MSCs: Successful fusion of MSCs with β-cells results in a β-cell like phenotype. Oncotarget 2016; 7(31): 48963-77. doi: 10.18632/oncotarget.10214 PMID: 27374092
  27. Amer MG, Embaby AS, Karam RA, Amer MG. Role of adipose tissue derived stem cells differentiated into insulin producing cells in the treatment of type I diabetes mellitus. Gene 2018; 654: 87-94. doi: 10.1016/j.gene.2018.02.008 PMID: 29452233
  28. Chen YJ, Finkbeiner SR, Weinblatt D, et al. De novo formation of insulin-producing "neo-β cell islets" from intestinal crypts. Cell Rep 2014; 6(6): 1046-58. doi: 10.1016/j.celrep.2014.02.013 PMID: 24613355
  29. Boumaza I, Srinivasan S, Witt WT, et al. Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia. J Autoimmun 2009; 32(1): 33-42. doi: 10.1016/j.jaut.2008.10.004 PMID: 19062254
  30. Gao X, Song L, Shen K, et al. Bone marrow mesenchymal stem cells promote the repair of islets from diabetic mice through paracrine actions. Mol Cell Endocrinol 2014; 388(1-2): 41-50. doi: 10.1016/j.mce.2014.03.004 PMID: 24667703
  31. Chen LB, Jiang XB, Yang L. Differentiation of rat marrow mesenchymal stem cells into pancreatic islet beta-cells. World J Gastroenterol 2004; 10(20): 3016-20. doi: 10.3748/wjg.v10.i20.3016 PMID: 15378785
  32. Guan R, Purohit S, Wang H, et al. Chemokine (C-C motif) ligand 2 (CCL2) in sera of patients with type 1 diabetes and diabetic complications. PLoS One 2011; 6(4): e17822. doi: 10.1371/journal.pone.0017822 PMID: 21532752
  33. Petropavlovskaia M, Makhlin J, Sampalis J, Rosenberg L. Development of an in vitro pancreatic tissue model to study regulation of islet neogenesis associated protein expression. J Endocrinol 2006; 191(1): 65-81. doi: 10.1677/joe.1.06800 PMID: 17065390
  34. Tran DT, Pottekat A, Lee K, et al. Inflammatory cytokines rewire the proinsulin interaction network in human islets. J Clin Endocrinol Metab 2022; 107(11): 3100-10. doi: 10.1210/clinem/dgac493 PMID: 36017587
  35. Hundhausen C, Roth A, Whalen E, Chen J, Schneider A, Long AS, et al. Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression. Sci Transl Med 2017; 48(356): 995-1002. PMID: 27629486
  36. Kuriya G, Uchida T, Akazawa S, et al. Double deficiency in IL-17 and IFN-γ signalling significantly suppresses the development of diabetes in the NOD mouse. Diabetologia 2013; 56(8): 1773-80. doi: 10.1007/s00125-013-2935-8 PMID: 23699989
  37. Ferreira RC, Simons HZ, Thompson WS, et al. IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients. Diabetologia 2015; 58(4): 781-90. doi: 10.1007/s00125-015-3509-8 PMID: 25652388
  38. Sutherland APR, Van Belle T, Wurster AL, et al. Interleukin-21 is required for the development of type 1 diabetes in NOD mice. Diabetes 2009; 58(5): 1144-55. doi: 10.2337/db08-0882 PMID: 19208913
  39. Wan XX, Zhang DY, Khan MA, et al. Stem cell transplantation in the treatment of type 1 Diabetes Mellitus: From insulin replacement to beta-cell replacement. Front Endocrinol 2022; 13: 859638. doi: 10.3389/fendo.2022.859638 PMID: 35370989
  40. Silva IBB, Kimura CH, Colantoni VP, Sogayar MC. Stem cells differentiation into insulin-producing cells (IPCs): Recent advances and current challenges. Stem Cell Res Ther 2022; 13(1): 309. doi: 10.1186/s13287-022-02977-y PMID: 35840987
  41. Azizi Z, Abbaszadeh R, Sahebnasagh R, Norouzy A, Motevaseli E, Maedler K. Bone marrow mesenchymal stromal cells for diabetes therapy: Touch, fuse, and fix? Stem Cell Res Ther 2022; 13(1): 348. doi: 10.1186/s13287-022-03028-2 PMID: 35883121
  42. Bourgeois S, Sawatani T, Van Mulders A, et al. Towards a functional cure for diabetes using stem cell-derived beta cells: Are we there yet? Cells 2021; 10(1): 191. doi: 10.3390/cells10010191 PMID: 33477961
  43. de Klerk E, Hebrok M. Stem cell-based clinical trials for diabetes mellitus. Front Endocrinol 2021; 12: 631463. doi: 10.3389/fendo.2021.631463 PMID: 33716982
  44. Ryba-Stanisławowska M, Rybarczyk-Kapturska K, Myśliwiec M, Myśliwska J. Elevated levels of serum IL-12 and IL-18 are associated with lower frequencies of CD4(+)CD25 (high)FOXP3 (+) regulatory Tcells in young patients with type 1 diabetes. Inflammation 2014; 37(5): 1513-20. doi: 10.1007/s10753-014-9878-1 PMID: 24677179
  45. Homann D. Back from the brink: The uses of targeting the CXCL10:CXCR3 axis in Type 1 Diabetes. Diabetes 2015; 64(12): 3990-2. doi: 10.2337/dbi15-0019 PMID: 26604174

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers