Hematopoietic Stem Cells in Type 1 Diabetes

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Jul 26

PMID 34305929

Citations 5

Authors

Ida Pastore

Emma Assi

Moufida Ben Nasr

Andrea Mario Bolla

Anna Maestroni

Vera Usuelli

Cristian Loretelli

Andy Joe Seelam

Ahmed Abdelsalam

Gian Vincenzo Zuccotti

Francesca DAddio

Paolo Fiorina

Affiliations

Soon will be listed here.

Abstract

Despite the increasing knowledge of pathophysiological mechanisms underlying the onset of type 1 diabetes (T1D), the quest for therapeutic options capable of delaying/reverting the diseases is still ongoing. Among all strategies currently tested in T1D, the use of hematopoietic stem cell (HSC)-based approaches and of teplizumab, showed the most encouraging results. Few clinical trials have already demonstrated the beneficial effects of HSCs in T1D, while the durability of the effect is yet to be established. Investigators are also trying to understand whether the use of selected and better-characterized HSCs subsets may provide more benefits with less risks. Interestingly, manipulated HSCs showed promising results in murine models and the recent introduction of the humanized mouse models accelerated the translational potentials of such studies and their final road to clinic. Indeed, immunomodulatory as well as trafficking abilities can be enhanced in genetically modulated HSCs and genetically engineered HSCs may be viewed as a novel "biologic" therapy, to be further tested and explored in T1D and in other autoimmune/immune-related disorders.

Citing Articles

Potentials of bone marrow cells-derived from naïve or diabetic mice in autoimmune type 1 diabetes: immunomodulatory, anti-inflammatory, anti hyperglycemic, and antioxidative.

Gomaa S, Nassef M, Hafez A Endocrine. 2024; 86(3):959-979.

PMID: 39014283 PMC: 11554735. DOI: 10.1007/s12020-024-03929-7.

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.

Monitoring of Autoantibodies Following Autologous Hematopoietic Stem Cell Transplantation in 6 Children with Recently Diagnosed Type 1 Diabetes Mellitus.

Mesples A, Cox D, Lundy H, Antonio-Collie S, Diggiss C, Lakey J Med Sci Monit. 2023; 29:e938979.

PMID: 36659834 PMC: 9872439. DOI: 10.12659/MSM.938979.

Benefits and Hurdles of Pancreatic β-Cell Replacement.

Bolla A, Montefusco L, Pastore I, Lunati M, Ben Nasr M, Fiorina P Stem Cells Transl Med. 2022; 11(10):1029-1039.

PMID: 36073717 PMC: 9585952. DOI: 10.1093/stcltm/szac058.

Stem Cell Transplantation in the Treatment of Type 1 Diabetes Mellitus: From Insulin Replacement to Beta-Cell Replacement.

Wan X, Zhang D, Khan M, Zheng S, Hu X, Zhang Q Front Endocrinol (Lausanne). 2022; 13:859638.

PMID: 35370989 PMC: 8972968. DOI: 10.3389/fendo.2022.859638.

References

Shultz L, Brehm M, Garcia-Martinez J, Greiner D . Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol. 2012; 12(11):786-98. PMC: 3749872. DOI: 10.1038/nri3311. View

Lutter L, Spierings J, van Rhijn-Brouwer F, van Laar J, van Wijk F . Resetting the T Cell Compartment in Autoimmune Diseases With Autologous Hematopoietic Stem Cell Transplantation: An Update. Front Immunol. 2018; 9:767. PMC: 5920130. DOI: 10.3389/fimmu.2018.00767. View

van Laar J, Farge D, Sont J, Naraghi K, Marjanovic Z, Larghero J . Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA. 2014; 311(24):2490-8. DOI: 10.1001/jama.2014.6368. View

Ben Nasr M, DAddio F, Malvandi A, Faravelli S, Castillo-Leon E, Usuelli V . Prostaglandin E2 Stimulates the Expansion of Regulatory Hematopoietic Stem and Progenitor Cells in Type 1 Diabetes. Front Immunol. 2018; 9:1387. PMC: 6018202. DOI: 10.3389/fimmu.2018.01387. View

Masiuk K, Laborada J, Roncarolo M, Hollis R, Kohn D . Lentiviral Gene Therapy in HSCs Restores Lineage-Specific Foxp3 Expression and Suppresses Autoimmunity in a Mouse Model of IPEX Syndrome. Cell Stem Cell. 2019; 24(2):309-317.e7. DOI: 10.1016/j.stem.2018.12.003. View

Snarski E, Milczarczyk A, Torosian T, Paluszewska M, Urbanowska E, Krol M . Independence of exogenous insulin following immunoablation and stem cell reconstitution in newly diagnosed diabetes type I. Bone Marrow Transplant. 2010; 46(4):562-6. DOI: 10.1038/bmt.2010.147. View

Walicka M, Milczarczyk A, Snarski E, Jedynasty K, Halaburda K, Torosian T . Lack of persistent remission following initial recovery in patients with type 1 diabetes treated with autologous peripheral blood stem cell transplantation. Diabetes Res Clin Pract. 2018; 143:357-363. DOI: 10.1016/j.diabres.2018.07.020. View

Sun S, Gao Y, Liu G, Li Y, Gao W, Ran X . Efficacy and Safety of Stem Cell Therapy for T1DM: An Updated Systematic Review and Meta-Analysis. J Diabetes Res. 2020; 2020:5740923. PMC: 7569432. DOI: 10.1155/2020/5740923. View

van Megen K, van t Wout E, Forman S, Roep B . A Future for Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes. Front Immunol. 2018; 9:690. PMC: 5904498. DOI: 10.3389/fimmu.2018.00690. View

10.

Fiorina P, Voltarelli J, Zavazava N . Immunological applications of stem cells in type 1 diabetes. Endocr Rev. 2011; 32(6):725-54. PMC: 3591677. DOI: 10.1210/er.2011-0008. View

11.

Cantu-Rodriguez O, Lavalle-Gonzalez F, Herrera-Rojas M, Jaime-Perez J, Hawing-Zarate J, Gutierrez-Aguirre C . Long-Term Insulin Independence in Type 1 Diabetes Mellitus Using a Simplified Autologous Stem Cell Transplant. J Clin Endocrinol Metab. 2016; 101(5):2141-8. DOI: 10.1210/jc.2015-2776. View

12.

DAddio F, Valderrama Vasquez A, Ben Nasr M, Franek E, Zhu D, Li L . Autologous nonmyeloablative hematopoietic stem cell transplantation in new-onset type 1 diabetes: a multicenter analysis. Diabetes. 2014; 63(9):3041-6. DOI: 10.2337/db14-0295. View

13.

Delemarre E, van den Broek T, Mijnheer G, Meerding J, Wehrens E, Olek S . Autologous stem cell transplantation aids autoimmune patients by functional renewal and TCR diversification of regulatory T cells. Blood. 2015; 127(1):91-101. DOI: 10.1182/blood-2015-06-649145. View

14.

Herold K, Bundy B, Long S, Bluestone J, DiMeglio L, Dufort M . An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med. 2019; 381(7):603-613. PMC: 6776880. DOI: 10.1056/NEJMoa1902226. View

15.

Delovitch T, Singh B . The nonobese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD. Immunity. 1998; 7(6):727-38. DOI: 10.1016/s1074-7613(00)80392-1. View

16.

Greiner D, Brehm M, Hosur V, Harlan D, Powers A, Shultz L . Humanized mice for the study of type 1 and type 2 diabetes. Ann N Y Acad Sci. 2012; 1245:55-8. PMC: 3384500. DOI: 10.1111/j.1749-6632.2011.06318.x. View

17.

Alexander T, Farge D, Badoglio M, Lindsay J, Muraro P, Snowden J . Hematopoietic stem cell therapy for autoimmune diseases - Clinical experience and mechanisms. J Autoimmun. 2018; 92:35-46. DOI: 10.1016/j.jaut.2018.06.002. View

18.

Ye L, Li L, Wan B, Yang M, Hong J, Gu W . Immune response after autologous hematopoietic stem cell transplantation in type 1 diabetes mellitus. Stem Cell Res Ther. 2017; 8(1):90. PMC: 5395765. DOI: 10.1186/s13287-017-0542-1. View

19.

Copelan E . Hematopoietic stem-cell transplantation. N Engl J Med. 2006; 354(17):1813-26. DOI: 10.1056/NEJMra052638. View

20.

Zhang M, Racine J, Lin Q, Liu Y, Tang S, Qin Q . MHC-mismatched mixed chimerism restores peripheral tolerance of noncross-reactive autoreactive T cells in NOD mice. Proc Natl Acad Sci U S A. 2018; 115(10):E2329-E2337. PMC: 5877958. DOI: 10.1073/pnas.1720169115. View