Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

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

Review Article

Mesenchymal Stem Cell Therapy for Treating the Underlying Causes of Diabetes Mellitus and Its Consequences

Author(s): Diana Esquivel, Rangnath Mishra and Anand Srivastava*

Volume 19, Issue 5, 2024

Published on: 12 May, 2023

Page: [662 - 668] Pages: 7

DOI: 10.2174/1574888X18666230411111320

Price: $65

conference banner
Abstract

Diabetes mellitus (DM) is a multifaceted pathological condition, which at present is being considered an epidemic disease keeping the rampant rate of its increase in almost all population groups of the world in consideration. Out of the two types of DM described, T1D is characterized as an autoimmune condition that leads to the destruction of pancreatic β-cells by macrophages and T-cells, thereby, adversely affecting the production of insulin. On the other hand, T2D, often caused by insulin resistance, is commonly related to unhealthy habits, and therefore, it can be prevented in most cases. In both of the conditions, high levels of proinflammatory cytokines like IL-6, TNF-α, and INF-ƴ, lead to chronic inflammation, and elevated oxidative stress resulting in apoptosis and destruction of tissues. Although several treatments are available to treat the symptoms, the underlying causes are not well addressed. One of the most promising approaches to tackle the ill effects and the primary causes of DM is mesenchymal stem cell (MSC) therapy. The use of MSC therapy, because of the immunomodulatory and regenerative properties recorded in this type of cells in a number of experiments carried out in animal models and clinical trials of the disease, has reported positive outcomes. This review covers the principal mechanisms of action induced during MSC therapy in reference to the described pathophysiological pathways of both T1D and T2D. In addition, how this therapeutic intervention can counteract the ill effects of this condition leading to the promotion of tissue regeneration has been covered.

Graphical Abstract

[1]
Memon B, Abdelalim EM. Stem cell therapy for diabetes: Beta cells versus pancreatic progenitors. Cells 2020; 9(2): 283.
[http://dx.doi.org/10.3390/cells9020283] [PMID: 31979403]
[2]
Eizirik DL, Pasquali L, Cnop M. Pancreatic β-cells in type 1 and type 2 diabetes mellitus: Different pathways to failure. Nat Rev Endocrinol 2020; 16(7): 349-62.
[http://dx.doi.org/10.1038/s41574-020-0355-7] [PMID: 32398822]
[3]
Centers for Disease Control and Prevention. National Diabetes Statistics Report. 2021. Available from: https://www.cdc.gov/diabetes/data/statistics-report/index.html
[4]
Herold KC, Bundy BN, Long SA, et al. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med 2019; 381(7): 603-13.
[http://dx.doi.org/10.1056/NEJMoa1902226] [PMID: 31180194]
[5]
Ley SH, Hamdy O, Mohan V, Hu FB. Prevention and management of type 2 diabetes: Dietary components and nutritional strategies. Lancet 2014; 383(9933): 1999-2007.
[http://dx.doi.org/10.1016/S0140-6736(14)60613-9] [PMID: 24910231]
[6]
Pittenger MF, Discher DE, Péault BM, Phinney DG, Hare JM, Caplan AI. Mesenchymal stem cell perspective: Cell biology to clinical progress. NPJ Regen Med 2019; 4(1): 22.
[http://dx.doi.org/10.1038/s41536-019-0083-6] [PMID: 31815001]
[7]
Müller L, Tunger A, Wobus M, et al. Immunomodulatory properties of mesenchymal stromal cells: An update. Front Cell Dev Biol 2021; 9: 637725.
[http://dx.doi.org/10.3389/fcell.2021.637725] [PMID: 33634139]
[8]
American Diabetes Association Diabetes. Consulted on American Diabetes Association | Research, Education. Advocacy 2022.
[9]
Xing Y, Hogquist KA. T-cell tolerance: Central and peripheral. Cold Spring Harb Perspect Biol 2012; 4(6): a006957.
[http://dx.doi.org/10.1101/cshperspect.a006957] [PMID: 22661634]
[10]
Cnop M, Welsh N, Jonas JC, Jörns A, Lenzen S, Eizirik DL. Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: Many differences, few similarities. Diabetes 2005; 54(S2): S97-S107.
[http://dx.doi.org/10.2337/diabetes.54.suppl_2.S97] [PMID: 16306347]
[11]
Paschou SA, Papadopoulou-Marketou N, Chrousos GP, Kanaka-Gantenbein C. On type 1 diabetes mellitus pathogenesis. Endocr Connect 2018; 7(1): R38-46.
[http://dx.doi.org/10.1530/EC-17-0347] [PMID: 29191919]
[12]
Pérez De Nanclares G, Bilbao JR, Calvo B, Vitoria JC, Vázquez F, Castaño L. 5′-Insulin gene VNTR polymorphism is specific for type 1 diabetes: No association with celiac or Addison’s disease. Ann N Y Acad Sci 2003; 1005(1): 319-23.
[http://dx.doi.org/10.1196/annals.1288.050] [PMID: 14679083]
[13]
Durinovic-Belló I, Jelinek E, Schlosser M, et al. Class III alleles at the insulin VNTR polymorphism are associated with regulatory T-cell responses to proinsulin epitopes in HLA-DR4, DQ8 individuals. Diabetes 2005; 54(S2): S18-24.
[http://dx.doi.org/10.2337/diabetes.54.suppl_2.S18] [PMID: 16306335]
[14]
Gavin PG, Hamilton-Williams EE. The gut microbiota in type 1 diabetes: Friend or foe? Curr Opin Endocrinol Diabetes Obes 2019; 26(4): 207-12.
[http://dx.doi.org/10.1097/MED.0000000000000483] [PMID: 31145129]
[15]
Dotta F, Censini S, van Halteren AGS, et al. Coxsackie B4 virus infection of β cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc Natl Acad Sci USA 2007; 104(12): 5115-20.
[http://dx.doi.org/10.1073/pnas.0700442104] [PMID: 17360338]
[16]
Fu Z, Gilbert ER, Liu D. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr Diabetes Rev 2013; 9(1): 25-53.
[http://dx.doi.org/10.2174/157339913804143225] [PMID: 22974359]
[17]
Galicia-Garcia U, Benito-Vicente A, Jebari S, et al. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci 2020; 21(17): 6275.
[http://dx.doi.org/10.3390/ijms21176275] [PMID: 32872570]
[18]
Uusitupa M, Khan TA, Viguiliouk E, et al. Prevention of type 2 diabetes by lifestyle changes: A systematic review and meta-analysis. Nutrients 2019; 11(11): 2611.
[http://dx.doi.org/10.3390/nu11112611] [PMID: 31683759]
[19]
Mishra S, Pericherla S, Manthuruthil S, Mishra S, Hanno R. Effect of physical activity on insulin resistance, inflammation and oxidative stress in diabetes mellitus. J Clin Diagn Res 2013; 7(8): 1764-6.
[http://dx.doi.org/10.7860/JCDR/2013/6518.3306] [PMID: 24086908]
[20]
Roden M, Shulman GI. The integrative biology of type 2 diabetes. Nature 2019; 576(7785): 51-60.
[http://dx.doi.org/10.1038/s41586-019-1797-8] [PMID: 31802013]
[21]
Neis E, Dejong C, Rensen S. The role of microbial amino acid metabolism in host metabolism. Nutrients 2015; 7(4): 2930-46.
[http://dx.doi.org/10.3390/nu7042930] [PMID: 25894657]
[22]
Li X, Watanabe K, Kimura I. Gut microbiota dysbiosis drives and implies novel therapeutic strategies for diabetes mellitus and related metabolic diseases. Front Immunol 2017; 8: 1882.
[http://dx.doi.org/10.3389/fimmu.2017.01882] [PMID: 29326727]
[23]
Montgomery MK, Turner N. Mitochondrial dysfunction and insulin resistance: An update. Endocr Connect 2015; 4(1): R1-R15.
[http://dx.doi.org/10.1530/EC-14-0092] [PMID: 25385852]
[24]
Pinti MV, Fink GK, Hathaway QA, Durr AJ, Kunovac A, Hollander JM. Mitochondrial dysfunction in type 2 diabetes mellitus: An organ-based analysis. Am J Physiol Endocrinol Metab 2019; 316(2): E268-85.
[http://dx.doi.org/10.1152/ajpendo.00314.2018] [PMID: 30601700]
[25]
McCall AL, Farhy LS. Treating type 1 diabetes: From strategies for insulin delivery to dual hormonal control. Minerva Endocrinol 2013; 38(2): 145-63.
[PMID: 23732369]
[26]
Mo Y, Wang Z, Gao J, et al. Comparative study of three types of mesenchymal stem cell to differentiate into pancreatic β like cells in vitro. Exp Ther Med 2021; 22(3): 936.
[http://dx.doi.org/10.3892/etm.2021.10368] [PMID: 34335885]
[27]
Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM. A new mesenchymal stem cell (MSC) paradigm: Polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One 2010; 5(4): e10088.
[http://dx.doi.org/10.1371/journal.pone.0010088] [PMID: 20436665]
[28]
Mishra VK, Shih HH, Parveen F, et al. Identifying the therapeutic significance of mesenchymal stem cells. Cells 2020; 9(5): 1145.
[http://dx.doi.org/10.3390/cells9051145] [PMID: 32384763]
[29]
Khatri R, Mazurek S, Petry SF, Linn T. Mesenchymal stem cells promote pancreatic β-cell regeneration through downregulation of FoxO1 pathway. Stem Cell Res Ther 2020; 11(1): 497.
[http://dx.doi.org/10.1186/s13287-020-02007-9] [PMID: 33239104]
[30]
Zhou T, Yuan Z, Weng J, et al. Challenges and advances in clinical applications of mesenchymal stromal cells. J Hematol Oncol 2021; 14(1): 24.
[http://dx.doi.org/10.1186/s13045-021-01037-x] [PMID: 33579329]
[31]
Dang LTT, et al. Intravenous infusion of human adipose tissue-derived mesenchymal stem cells to treat type 1 diabetic mellitus in mice: An evaluation of grafted cell doses.Stem Cells: Biology and Engineering Advances in Experimental Medicine and Biology. Cham: Springer 2017; p. 1083.
[http://dx.doi.org/10.1007/5584_2017_127]
[32]
Sun J, Ni Q, Xie J, et al. β-Cell dedifferentiation in patients with t2d with adequate glucose control and nondiabetic chronic pancreatitis. J Clin Endocrinol Metab 2019; 104(1): 83-94.
[http://dx.doi.org/10.1210/jc.2018-00968] [PMID: 30085195]
[33]
Wang L, Liu T, Liang R, et al. Mesenchymal stem cells ameliorate β cell dysfunction of human type 2 diabetic islets by reversing β cell dedifferentiation. EBioMedicine 2020; 51: 102615.
[http://dx.doi.org/10.1016/j.ebiom.2019.102615] [PMID: 31918404]
[34]
Huang Q, Huang Y, Liu J. Mesenchymal stem Cells: An excellent candidate for the treatment of diabetes mellitus. Int J Endocrinol 2021; 2021: 9938658.
[http://dx.doi.org/10.1155/2021/9938658] [PMID: 34135959]
[35]
Nie P, Bai X, Lou Y, et al. Human umbilical cord mesenchymal stem cells reduce oxidative damage and apoptosis in diabetic nephropathy by activating Nrf2. Stem Cell Res Ther 2021; 12(1): 450.
[http://dx.doi.org/10.1186/s13287-021-02447-x] [PMID: 34380544]
[36]
Sávio-Silva C, Soinski-Sousa PE, Simplício-Filho A, Bastos RMC, Beyerstedt S, Rangel ÉB. Therapeutic potential of mesenchymal stem cells in a pre-clinical model of diabetic kidney disease and obesity. Int J Mol Sci 2021; 22(4): 1546.
[http://dx.doi.org/10.3390/ijms22041546] [PMID: 33557007]
[37]
Khatri R, Petry SF, Linn T. Intrapancreatic MSC transplantation facilitates pancreatic islet regeneration. Stem Cell Res Ther 2021; 12(1): 121.
[http://dx.doi.org/10.1186/s13287-021-02173-4] [PMID: 33579357]
[38]
Si Y, Zhao Y, Hao H, et al. Infusion of mesenchymal stem cells ameliorates hyperglycemia in type 2 diabetic rats: Identification of a novel role in improving insulin sensitivity. Diabetes 2012; 61(6): 1616-25.
[http://dx.doi.org/10.2337/db11-1141] [PMID: 22618776]
[39]
Lv W, Graves DT, He L, et al. Depletion of the diabetic gut microbiota resistance enhances stem cells therapy in type 1 diabetes mellitus. Theranostics 2020; 10(14): 6500-16.
[http://dx.doi.org/10.7150/thno.44113] [PMID: 32483466]
[40]
Nojehdehi S, Soudi S, Hesampour A, Rasouli S, Soleimani M, Hashemi SM. Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type-1 autoimmune diabetes. J Cell Biochem 2018; 119(11): 9433-43.
[http://dx.doi.org/10.1002/jcb.27260] [PMID: 30074271]
[41]
Phinney DG, Pittenger MF. Concise review: MSC-derived exosomes for cell-free therapy. Stem Cells 2017; 35(4): 851-8.
[http://dx.doi.org/10.1002/stem.2575] [PMID: 28294454]
[42]
Lee BC, Kang I, Yu KR. Therapeutic features and updated clinical trials of mesenchymal stem cell (msc)-derived exosomes. J Clin Med 2021; 10(4): 711.
[http://dx.doi.org/10.3390/jcm10040711] [PMID: 33670202]
[43]
Lee KO, Gan SU, Calne RY. Stem cell therapy for diabetes. Indian J Endocrinol Metab 2012; 16(8): 227.
[http://dx.doi.org/10.4103/2230-8210.104045] [PMID: 23565384]
[44]
Parrotta E, De Angelis MT, Scalise S, et al. Two sides of the same coin? Unraveling subtle differences between human embryonic and induced pluripotent stem cells by Raman spectroscopy. Stem Cell Res Ther 2017; 8(1): 271.
[http://dx.doi.org/10.1186/s13287-017-0720-1] [PMID: 29183402]
[45]
Hua X, Wang Y, Tang Y, et al. Pancreatic insulin-producing cells differentiated from human embryonic stem cells correct hyperglycemia in SCID/NOD mice, an animal model of diabetes. PLoS One 2014; 9(7): e102198.
[http://dx.doi.org/10.1371/journal.pone.0102198] [PMID: 25009980]
[46]
Alipio Z, Liao W, Roemer EJ, et al. Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic β-like cells. Proc Natl Acad Sci 2010; 107(30): 13426-31.
[http://dx.doi.org/10.1073/pnas.1007884107] [PMID: 20616080]
[47]
Ezquer ME, Ezquer FE, Arango-Rodríguez ML, Conget PA. MSC transplantation: A promising therapeutic strategy to manage the onset and progression of diabetic nephropathy. Biol Res 2012; 45(3): 289-96.
[http://dx.doi.org/10.4067/S0716-97602012000300010] [PMID: 23283438]
[48]
Wang M, Song L, Strange C, Dong X, Wang H. Therapeutic effects of adipose stem cells from diabetic mice for the treatment of type 2 diabetes. Mol Ther 2018; 26(8): 1921-30.
[http://dx.doi.org/10.1016/j.ymthe.2018.06.013] [PMID: 30005867]
[49]
Qi Y, Ma J, Li S, Liu W. Applicability of adipose-derived mesenchymal stem cells in treatment of patients with type 2 diabetes. Stem Cell Res Ther 2019; 10(1): 274.
[http://dx.doi.org/10.1186/s13287-019-1362-2] [PMID: 31455405]
[50]
Ikemoto T, Tokuda K, Wada Y, et al. Adipose tissue from type 1 diabetes mellitus patients can be used to generate insulin-producing cells. Pancreas 2020; 49(9): 1225-31.
[http://dx.doi.org/10.1097/MPA.0000000000001663] [PMID: 32898009]

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