Advances in Stem Cell Therapy for Type 2 Diabetes Mellitus
Main Article Content
Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder marked by insulin resistance and impaired insulin secretion, resulting in hyperglycemia and microvascular complications. Conventional treatments, such as lifestyle changes and pharmacotherapy, often fail to provide optimal glycemic control or prevent complications.
Recent advances in stem cell therapy, particularly involving mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs), have shown promise in reducing blood glucose levels, improving glycated hemoglobin (HbA1c), and addressing microvascular and macrovascular complications without promising a cure for this chronic illness.
Many biotechnological advances have set up T2DM among its targeted conditions. To mention a few, 3D bioprinting and gene therapy are being exploited to enhance stem cell applications.
Though a cure for diabetes remains out of sight, significant progress has been made through these novel approaches. Early clinical trials demonstrate improved glycemic control, insulin independence, and enhanced beta-cell survival all leading a path to control the devastations of T2DM complications.
Advanced stem cell therapies, including the differentiation or reprogramming of embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), MSCs, and marrow-derived stem cells (MDSCs) into beta islet cells, offer other innovative avenues.
In addition to reviewing the recent advances in stem cell therapies in this field, we explore the impact of stem cell differentiation on diabetic complications like nephropathy, neuropathy, retinopathy, and cardiovascular diseases, and the challenges of scalability, safety, and regulatory hurdles. The role of gene editing with CRISPR-Cas9 and the potential of 3D bioprinting, the mechanisms implicated such as direct differentiation, immune modulation, tissue repair, and paracrine effects are also examined.
Keywords:
Type 2 diabetes Mellitus, Mesenchymal Stem Cells, Hematopoietic Stem cells, Bioprinting, Gene therapy
Article Details
How to Cite
BTERRANI, Elie et al.
Advances in Stem Cell Therapy for Type 2 Diabetes Mellitus.
Medical Research Archives, [S.l.], v. 12, n. 12, jan. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6174>. Date accessed: 09 apr. 2025.
doi: https://doi.org/10.18103/mra.v12i12.6174.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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15. Wehbe T, Chahine NA, Sissi S, et al. Bone marrow derived stem cell therapy for type 2 diabetes mellitus. Stem Cell Investig. 2016 Dec 6;3:87.
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22. Bhansali S, Dutta P, Kumar V, et al. Efficacy of autologous bone marrow-derived mesenchymal stem cell and mononuclear cell transplantation in type 2 diabetes mellitus: a randomized placebo-controlled comparative study. Stem Cells Dev. 2017;26(7):471–481.
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27. Gao, D., Gu, C., Wu, Y., et al. (2014). Mesenchymal stromal cells enhance wound healing by ameliorating impaired metabolism in diabetic mice. Cytotherapy 16 (11), 1467–1475.
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29. Lee KO, Gan SU, Calne RY. Stem cell therapy for diabetes. Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S227-9.
30. Mathur A, Taurin S, Alshammary S. The Safety and Efficacy of Mesenchymal Stem Cells in the Treatment of Type 2 Diabetes- A Literature Review. Diabetes Metab Syndr Obes. 2023 Mar 14;16:769-777.
31. Chen XB, Fazel Anvari-Yazdi A, Duan X, et al. Biomaterials / bioinks and extrusion bioprinting. Bioact Mater. 2023 Jun 27;28:511-536.
32. Zang L, Li Y, Hao H, Liu J,et al. Efficacy and safety of umbilical cord-derived mesenchymal stem cells in Chinese adults with type 2 diabetes: a single-center, double-blinded, randomized, placebo-controlled phase II trial. Stem Cell Res Ther. 2022 May 3;13(1):180.
33. Lee M-Y, Huang J-C, Chen S-C, et al. Association of HbA1C variability and renal progression in patients with type 2 diabetes with chronic kidney disease stages 3–4. Int J Mol Sci. 2018; 19(12):4116. doi: 10.3390/ijms19124116 [DOI] [PMC free article] [PubMed] [Google Scholar]
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35. Moassesfar S, Masharani U, Frassetto LA, et al. A comparative analysis of the safety, efficacy, and cost of islet versus pancreas transplantation in nonuremic patients with type 1 diabetes. Am J Transplant. 2016;16(2):518–526.
36. Tan SY, Mei Wong JL, Sim YJ, et al. Type 1 and 2 diabetes mellitus: A review on current treatment approach and gene therapy as potential intervention. Diabetes Metab Syndr. 2019 Jan-Feb;13(1):364-372.
37. Hamad FR, Rahat N, Shankar K, et al. Efficacy of stem cell application in diabetes mellitus: promising future therapy for diabetes and its complications. Cureus. 2021;13(2):e13563.
38. Moreira A, Kahlenberg S, Hornsby P. Therapeutic potential of mesenchymal stem cells for diabetes. J Mol Endocrinol. 2017;59(3):R109–r120.
39. Loukelis K, Koutsomarkos N, Mikos AG, Chatzinikolaidou M. Advances in 3D bioprinting for regenerative medicine applications. Regen Biomater. 2024 Mar 26;11:rbae033.
40. Konstantinos Loukelis, Nikos Koutsomarkos, , et al. The cutting‐edge progress in bioprinting for biomedicine: principles, applications, and future perspectives. Regen Biomater. 2024; 11.
41. Shuge Liu, Yating Chen, Zhiyao Wang, et.al. The cutting‐edge progress in bioprinting for biomedicine: principles, applications, and future perspectives MedComm (2020) 2024 Oct; 5(10): e753. Published online 2024 Sep 23
42. Lee J., Cho J., D’Egidio F., Vignon C. , et al. "Probing multiple transplant delivery routes of CD+ 34 stem cells for promoting behavioral and histological benefits in experimental ischemic stroke." Stem Cells Translational Medicine 13, no. 2 (2024): 177-190.
43. Murugan, D., Mishra, P., Bhat, S.N., Pandey, V., Mallick, S.P., Guruprasad, K.P., Srivastava, P. and Singh, B.N., 2024. From shape to function—bioprinting technologies for tissue engineered grafts to meet clinical needs. International Journal of Polymeric Materials and Polymeric Biomaterials, 73(8), pp.701-722.
44. Mishra S, Tiwari P, Yadav R, Patel PS. An extensive analysis of diseases associated with diabetes. Journal of Pharma Insights and Research. 2024 Jun 14;2(3):174-87.
45. Huang M, Liu Y, Zhang L, Wang S, Wang X, He Z. Advancements in Research on Mesenchymal Stem-Cell-Derived Exosomal miRNAs: A Pivotal Insight into Aging and Age-Related Diseases. Biomolecules. 2024 Oct 24;14(11):1354.
2. International Diabetes Federation. (2019). IDF Diabetes Atlas (9th ed.).
3. Dabelea D, Rewers A, Stafford JM, et al.; Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for Diabetes in Youth Study. Pediatrics 2014;133:e938–e945.
4. Hope SV, Wienand-Barnett S, Shepherd M, et al. Practical classification guidelines for diabetes in patients treated with insulin: a cross-sectional study of the accuracy of diabetes diagnosis. Br J Gen Pract 2016;66:e315–e322
5. Zhong VW, Juhaeri J, Mayer-Davis EJ. Trends in hospital admission for diabetic ketoacidosis in adults with type 1 and type 2 diabetes in England, 1998–2013: a retrospective cohort study. Diabetes Care 2018;41:1870–1877
6. Skyler JS, Bakris GL, Bonifacio E, et al. Differentiation of diabetes by pathophysiology, natural history, and prognosis. Diabetes 2017; 66:241–255
7. Miclau K, Hambright WS, Huard J, Stoddart MJ, Bahney CS. Cellular expansion of MSCs: Shifting the regenerative potential. Aging Cell. 2023 Jan; 22(1):e13759.
8. Bin Jiang, Li Yan, Xiaoyan Wang, et al. Concise Review: Mesenchymal Stem Cells Derived from Human Pluripotent Cells, an Unlimited and Quality-Controllable Source for Therapeutic Applications, Stem Cells, Volume 37, Issue 5, May 2019, Pages 572–581.
9. Zhao, K., Liu, Q. The clinical application of mesenchymal stromal cells in hematopoietic stem cell transplantation. J Hematol Oncol 9, 46 (2016).
10. Yan D, Song Y, Zhang B , et al. Progress and application of adipose-derived stem cells in the treatment of diabetes and its complications. Stem Cell Res Ther. 2024 Jan 2;15(1):3.
11. Wang Y, Qiu F., Xu Y., et al, Stem cell-like memory T cells: The generation and application, Journal of Leukocyte Biology, Volume 110, Issue 6, December 2021, Pages 1209–1223
12. Zhu Y, Ge J, Huang C, Liu H, Jiang H. Application of mesenchymal stem cell therapy for aging frailty: from mechanisms to therapeutics. Theranostics. 2021 Mar 31;11(12):5675-5685.
13. Jiang R, Han Z, Zhuo G, et al. Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study. Front Med. 2011; 5(1):94–100.
14. Mathur A, Taurin S, Alshammary S. The Safety and Efficacy of Mesenchymal Stem Cells in the Treatment of Type 2 Diabetes- A Literature Review. Diabetes Metab Syndr Obes. 2023 Mar 14;16:769-777.
15. Wehbe T, Chahine NA, Sissi S, et al. Bone marrow derived stem cell therapy for type 2 diabetes mellitus. Stem Cell Investig. 2016 Dec 6;3:87.
16. Carulli E, Pompilio G, Vinci MC. Human Hematopoietic Stem/Progenitor Cells in Type One Diabetes Mellitus Treatment: Is There an Ideal Candidate? Cells. 2023 Mar 30;12(7):1054.
17. Schu S, Nosov M, O’Flynn L, et al. Immunogenicity of allogeneic mesenchymal stem cells. J Cell Mol Med. 2012;16(9):2094–2103. doi: 10.1111/j.1582-4934.2011.01509.x
18. 17.Nguyen LT, Hoang DM, Nguyen KT, et al. Type 2 diabetes mellitus duration and obesity alter the efficacy of autologously transplanted bone marrow-derived mesenchymal stem/stromal cells. Stem Cells Transl Med. 2021;10(9):1266–1278. doi: 10.1002/sctm.20-0506 [DOI] [PMC free article] [PubMed] [Google Scholar]
19. Wang L, Zhao S, Mao H, et al. Autologous bone marrow stem cell transplantation for the treatment of type 2 diabetes mellitus. Chin Med J. 2011;124(22):3622–3628.
20. Hu J, Wang Y, Gong H, et al. Long term effect and safety of Wharton’s jelly-derived mesenchymal stem cells on type 2 diabetes. Exp Ther Med. 2016;12(3):1857–1866.
21. Jiang R, Han Z, Zhuo G, et al. Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study. Front Med. 2011; 5(1):94–100.
22. Bhansali S, Dutta P, Kumar V, et al. Efficacy of autologous bone marrow-derived mesenchymal stem cell and mononuclear cell transplantation in type 2 diabetes mellitus: a randomized placebo-controlled comparative study. Stem Cells Dev. 2017;26(7):471–481.
23. Leighton E, Sainsbury CA, Jones GC. A Practical Review of C-Peptide Testing in Diabetes. Diabetes Ther. 2017;8(3):475–487.
24. Sherwani SI, Khan HA, Ekhzaimy A, et al. Significance of HbA1c test in diagnosis and prognosis of diabetic patients. Biomark Insights. 2016;11:BMI.S38440.
25. Wang, Y., Yi, H. & Song, Y. The safety of MSC therapy over the past 15 years: a meta-analysis. Stem Cell Res Ther 12, 545 (2021).
26. Kim M.J., Lee E.Y, You Y., Yang H.K., et al. Generation of iPSC-derived insulin-producing cells from patients with type 1 and type 2 diabetes compared with healthy control, Stem Cell Research, Volume 48, 2020.
27. Gao, D., Gu, C., Wu, Y., et al. (2014). Mesenchymal stromal cells enhance wound healing by ameliorating impaired metabolism in diabetic mice. Cytotherapy 16 (11), 1467–1475.
28. Giacco, F., and Brownlee, M. (2010). Oxidative stress and diabetic complications. Circ. Res. 107 (9), 1058–1070.
29. Lee KO, Gan SU, Calne RY. Stem cell therapy for diabetes. Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S227-9.
30. Mathur A, Taurin S, Alshammary S. The Safety and Efficacy of Mesenchymal Stem Cells in the Treatment of Type 2 Diabetes- A Literature Review. Diabetes Metab Syndr Obes. 2023 Mar 14;16:769-777.
31. Chen XB, Fazel Anvari-Yazdi A, Duan X, et al. Biomaterials / bioinks and extrusion bioprinting. Bioact Mater. 2023 Jun 27;28:511-536.
32. Zang L, Li Y, Hao H, Liu J,et al. Efficacy and safety of umbilical cord-derived mesenchymal stem cells in Chinese adults with type 2 diabetes: a single-center, double-blinded, randomized, placebo-controlled phase II trial. Stem Cell Res Ther. 2022 May 3;13(1):180.
33. Lee M-Y, Huang J-C, Chen S-C, et al. Association of HbA1C variability and renal progression in patients with type 2 diabetes with chronic kidney disease stages 3–4. Int J Mol Sci. 2018; 19(12):4116. doi: 10.3390/ijms19124116 [DOI] [PMC free article] [PubMed] [Google Scholar]
34. Berglund AK, Fortier LA, Antczak DF, et al. Immunoprivileged no more: measuring the immunogenicity of allogeneic adult mesenchymal stem cells. Stem Cell Res Ther. 2017;8(1):288.
35. Moassesfar S, Masharani U, Frassetto LA, et al. A comparative analysis of the safety, efficacy, and cost of islet versus pancreas transplantation in nonuremic patients with type 1 diabetes. Am J Transplant. 2016;16(2):518–526.
36. Tan SY, Mei Wong JL, Sim YJ, et al. Type 1 and 2 diabetes mellitus: A review on current treatment approach and gene therapy as potential intervention. Diabetes Metab Syndr. 2019 Jan-Feb;13(1):364-372.
37. Hamad FR, Rahat N, Shankar K, et al. Efficacy of stem cell application in diabetes mellitus: promising future therapy for diabetes and its complications. Cureus. 2021;13(2):e13563.
38. Moreira A, Kahlenberg S, Hornsby P. Therapeutic potential of mesenchymal stem cells for diabetes. J Mol Endocrinol. 2017;59(3):R109–r120.
39. Loukelis K, Koutsomarkos N, Mikos AG, Chatzinikolaidou M. Advances in 3D bioprinting for regenerative medicine applications. Regen Biomater. 2024 Mar 26;11:rbae033.
40. Konstantinos Loukelis, Nikos Koutsomarkos, , et al. The cutting‐edge progress in bioprinting for biomedicine: principles, applications, and future perspectives. Regen Biomater. 2024; 11.
41. Shuge Liu, Yating Chen, Zhiyao Wang, et.al. The cutting‐edge progress in bioprinting for biomedicine: principles, applications, and future perspectives MedComm (2020) 2024 Oct; 5(10): e753. Published online 2024 Sep 23
42. Lee J., Cho J., D’Egidio F., Vignon C. , et al. "Probing multiple transplant delivery routes of CD+ 34 stem cells for promoting behavioral and histological benefits in experimental ischemic stroke." Stem Cells Translational Medicine 13, no. 2 (2024): 177-190.
43. Murugan, D., Mishra, P., Bhat, S.N., Pandey, V., Mallick, S.P., Guruprasad, K.P., Srivastava, P. and Singh, B.N., 2024. From shape to function—bioprinting technologies for tissue engineered grafts to meet clinical needs. International Journal of Polymeric Materials and Polymeric Biomaterials, 73(8), pp.701-722.
44. Mishra S, Tiwari P, Yadav R, Patel PS. An extensive analysis of diseases associated with diabetes. Journal of Pharma Insights and Research. 2024 Jun 14;2(3):174-87.
45. Huang M, Liu Y, Zhang L, Wang S, Wang X, He Z. Advancements in Research on Mesenchymal Stem-Cell-Derived Exosomal miRNAs: A Pivotal Insight into Aging and Age-Related Diseases. Biomolecules. 2024 Oct 24;14(11):1354.