Comparative efficacy of regenerative therapies for β-cell preservation in diabetes mellitus: A meta-analysis

 Diabetes mellitus, which is associated with progressive loss of pancreatic β-cells, leading to insulin deficiency and hyperglycaemia, is of global health concern. Regenerative therapies, including stem cell therapies, have potential to address β-cell depletion and improve diabetes outcomes. The objective of this review was to compare the efficacy of stem cell-based regenerative therapies for the management of patients with both type 1 and type 2 diabetes mellitus. In carrying out this review, PubMed, ClinicalTrials.gov, and Google Scholar were the primary databases consulted. The analysis of 9 studies, including 5 randomised controlled trials and 4 non-randomised studies, revealed modest improvements in C-peptide levels, particularly in patients with type 2 diabetes mellitus, with a mean difference of 0.09 (95% confidence interval: -0.03, 0.21; p-value = 0.13), suggesting some benefit for β-cell preservation. However, the therapies did not show improvements in glycated haemoglobin levels, an increase in glycated haemoglobin level was observed, with a mean difference of 0.71 (95% confidence interval: 0.27, 1.15; p-value = 0.002), indicating worsening of glucose control, particularly in patients with type 2 diabetes mellitus. Although stem cell therapies show promise for β-cell preservation, such interventions do not appear to improve glycaemic control. This research has significant implications for clinicians involved in diabetes care, particularly those exploring regenerative treatments for type 1 and type 2 diabetes mellitus, and it underscores the necessity for personalised therapeutic strategies that account for the distinct pathophysiological mechanisms in these types of diabetes

stem cell therapy; regenerative medicine; C-peptide levels; HbA1C levels; glycaemic control

https://doi.org/10.63341/ijmmr/1.2026.32
  1. Chin SP, Kee LT, Mohd MA, Then KY. Umbilical cord-derived mesenchymal stem cells infusion in type 2 diabetes mellitus patients: A retrospective cytopeutics’ registry study. Diabetes Metab Syndr Obes. 2025:1643–59. DOI: 10.2147/dmso.s507801
  2. Izadi M, Sadr Hashemi Nejad A, Moazenchi M, Masoumi S, Rabbani A, Kompani F, et al. Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: A phase I/II randomised placebo-controlled clinical trial. Stem Cell Res Ther. 2022;13(1):264. DOI: 10.1186/s13287-022-02941-w
  3. Gao S, Zhang Y, Liang K, Bi R, Du Y. Mesenchymal stem cells (MSCs): A novel therapy for type 2 diabetes. Stem Cells Int. 2022;2022(1):8637493. DOI: 10.1155/2022/8637493
  4. Reichman TW, Markmann JF, Odorico J, Witkowski P, Fung JJ, Wijkstrom M, et al. Stem cell-derived, fully differentiated islets for type 1 diabetes. N Engl J Med. 2025;393:858–68. DOI: 10.1056/NEJMoa2506549
  5. Wei W, Li L, Deng L, Wang ZJ, Dong JJ, Lyu XY, et al. Autologous bone marrow mononuclear cell transplantation therapy improved symptoms in patients with refractory diabetic sensorimotor polyneuropathy via the mechanisms of paracrine and immunomodulation: A controlled study. Cell Transplant. 2020;29. DOI: 10.1177/0963689720949258
  6. Pires IG, e Souza JA, de Melo Bisneto AV, Passos XS, Carneiro CC. Clinical efficacy of stem-cell therapy on diabetes mellitus: A systematic review and meta-analysis. Transpl Immunol. 2022;75:101740. DOI: 10.1016/j.trim.2022.101740
  7. Zuo DB, Wang CH, Sang M, Sun XD, Chen GP, Ji KK. Stem cell therapy for diabetes: Advances, prospects, and challenges. World J Diabetes. 2025;16(7):107344. DOI: 10.4239/wjd.v16.i7.107344
  8. Zarei M, Sheikholeslami MA, Mozaffari M, Mortada Y. Innovative immunotherapies and emerging treatments in type 1 diabetes management. Diabet Epidemiol Manag. 2025;17:100247. DOI: 10.1016/j.deman.2024.100247
  9. Mouzzam AM, Ahmed A, Aamir A, Sharma G, Sarwath S, D’Moss J, et al. Stem cell therapy: A paradigm shift in reversing type 1 diabetes mellitus. Ann Med Surg. 2025;87(12):8556–62. DOI: 10.1097/ms9.0000000000004147
  10. Gieroba B, Kryska A, Sroka-Bartnicka A. Type 2 diabetes mellitus-conventional therapies and future perspectives in innovative treatment. Biochem Biophys Rep. 2025;42:102037. DOI: 10.1016/j.bbrep.2025.102037
  11. Nameghi SM. Exploring the recent advancements and prospects of personalised medicine in type 2 diabetes. Endocr Metab Sci. 2024;16:100193. DOI: 10.1016/j.endmts.2024.100193
  12. Hassanein A, Akhtar S. Recent advances in stem cell-based therapies for type 1 diabetes: A glimpse into the future. Biomol Biomed. 2025;26(1):5–23. DOI: 10.17305/bb.2025.12222
  13. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. DOI: 10.1136/bmj.n71
  14. Hosseini MS, Jahanshahlou F, Akbarzadeh MA, Zarei M, Vaez-Gharamaleki Y. Formulating research questions for evidence-based studies. J Med Surg Public Health. 2024;2:100046. DOI: 10.1016/j.glmedi.2023.100046
  15. Alharbi A, Stevenson M. Refining Boolean queries to identify relevant studies for systematic review updates. JAMIA. 2020;27(11):1658–66. DOI: 10.1093/jamia/ocaa148
  16. DeMars MM, Perruso C. MeSH and text-word search strategies: Precision, recall, and their implications for library instruction. JMLA. 2022;110(1):23. DOI: 10.5195/jmla.2022.1283
  17. Minozzi S, Dwan K, Borrelli F, Filippini G. Reliability of the revised Cochrane risk-of-bias tool for randomised trials (RoB2) improved with the use of implementation instruction. J Clin Epidemiol. 2022;141:99–105. DOI: 10.1016/j.jclinepi.2021.09.021
  18. Igelström E, Campbell M, Craig P, Katikireddi SV. Cochrane’s risk of bias tool for non-randomized studies (ROBINS-I) is frequently misapplied: A methodological systematic review. J Clin Epidemiol. 2021;140:22–32. DOI: 10.1016/j.jclinepi.2021.08.022
  19. Carlsson PO, Espes D, Sisay S, Davies LC, Smith CE, Svahn MG. Umbilical cord-derived mesenchymal stromal cells preserve endogenous insulin production in type 1 diabetes: A phase I/II randomised double-blind placebo-controlled trial. Diabetologia. 2023;66(8):1431–41. DOI: 10.1007/s00125-023-05934-3
  20. Wu Z, Huang S, Li S, Cai J, Huang L, Wu W, et al. Bone marrow mesenchymal stem cell and mononuclear cell combination therapy in patients with type 2 diabetes mellitus: A randomized controlled study with 8-year follow-up. Stem Cell Res Ther. 2024;15(1):339. DOI: 10.1186/s13287-024-03907-w
  21. Zang L, Li Y, Hao H, Liu J, Cheng Y, Li B, 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;13(1):180. DOI: 10.1186/s13287-022-02848-6
  22. Zang L, Li Y, Hao H, Liu J, Zhang Q, Gao F, et al. Efficacy of umbilical cord-derived mesenchymal stem cells in the treatment of type 2 diabetes assessed by retrospective continuous glucose monitoring. Stem Cells Transl Med. 2023;12(12):775–82. DOI: 10.1093/stcltm/szad060
  23. Lu J, Shen SM, Ling Q, Wang B, Li LR, Zhang W, et al. One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: An open parallel controlled clinical study. Stem Cell Res Ther. 2021;12(1):340. DOI: 10.1186/s13287-021-02417-3
  24. Raoufinia R, Tavakol-Afshari J, Afkhamizadeh M, Saburi E, Moghadam AA, Etemad S, et al. Safety and efficacy of allogeneic umbilical cord-derived mesenchymal stem cell transplantation in type 2 diabetes: A pilot clinical trial. Am J Stem Cells. 2025;14(4):244–60. DOI: 10.62347/ophf7871
  25. Lian XF, Lu DH, Liu HL, Liu YJ, Han XQ, Yang Y, et al. Effectiveness and safety of human umbilical cord-mesenchymal stem cells for treating type 2 diabetes mellitus. World J Diabetes. 2022;13(10):877–87. DOI: 10.4239/wjd.v13.i10.877
  26. Kumar N, Khan AA, Yadav A, Yadav S, Gautam BK, Rai RK, et al. Correlation of C-peptide levels with complications of type 2 diabetes mellitus. Cureus. 2025;17(10):e93754. DOI: 10.7759/cureus.93754
  27. Chen J, Huang Y, Liu C, Chi J, Wang Y, Xu L. The role of C-peptide in diabetes and its complications: An updated review. Front Endocrinol. 2023;14:1256093. DOI: 10.3389/fendo.2023.1256093
  28. Sayyed Kassem L, Rajpal A, Barreiro MV, Ismail‐Beigi F. Beta‐cell function in type 2 diabetes (T2DM): Can it be preserved or enhanced? J Diabetes. 2023;15(10):817–37. DOI: 10.1111/1753-0407.13446
  29. Janssen J, van den Berg E, Zinman B, Espeland MA, Geijselaers SLC, Mattheus M, et al. HbA1c, insulin resistance, and β-cell function in relation to cognitive function in type 2 diabetes: The Carolina cognition substudy. Diabetes Care. 2019;42(1):e1–3. DOI: 10.2337/dc18-0914
  30. Wu Q, Zheng S, Qin Y, Zheng X, Chen H, Yang T, et al. Efficacy and safety of stem cell transplantation in patients with type 1 diabetes – a systematic review and meta-analysis. Endocr J. 2020;67(8):827–40. DOI: 10.1507/endocrj.ej20-0050
  31. He J, Kong D, Yang Z, Guo R, Amponsah AE, Feng B, et al. Clinical efficacy on glycemic control and safety of mesenchymal stem cells in patients with diabetes mellitus: Systematic review and meta-analysis of RCT data. PloS One. 2021;16(3):e0247662. DOI: 10.1371/journal.pone.0247662
  32. Sun SY, Gao Y, Liu GJ, Li YK, Gao W, Ran XW. Efficacy and safety of stem cell therapy for T1DM: An updated systematic review and meta‐analysis. J Diabetes Res. 2020;1:5740923. DOI: 10.1155/2020/5740923
  33. Kashbour M, Abdelmalik A, Yassin MN, Abed M, Aldieb E, Abdullah DM, et al. Mesenchymal stem cell-based therapy for type 1 & 2 diabetes mellitus patients: A systematic review and meta-analysis of randomized controlled trials. Diabetol Metabol Syndr. 2025;17(1):189. DOI:10.1186/s13098-025-01619-6
  34. Bourgeois S, Coenen S, Degroote L, Willems L, Van Mulders A, Pierreux J, et al. Harnessing beta cell regeneration biology for diabetes therapy. Trends Endocrinol Metab. 2024;35(11):951–66. DOI: 10.1016/j.tem.2024.03.006
  35. Lansberry TR, Stabler CL. Immunoprotection of cellular transplants for autoimmune type 1 diabetes through local drug delivery. Adv Drug Deliv Rev. 2024;206:115179. DOI: 10.1016/j.addr.2024.115179
  36. Scherm MG, Wyatt RC, Serr I, Anz D, Richardson SJ, Daniel C. Beta cell and immune cell interactions in autoimmune type 1 diabetes: How they meet and talk to each other. Mol Metab. 2022;64:101565. DOI: 10.1016/j.molmet.2022.101565
  37. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci. 2020;21(17):6275. DOI: 10.3390/ijms21176275
  38. Yang N, Hickson LJ, Lerman LO. Stem cell therapy for type-2 diabetes: Keeping the pedal to the metal to deliver translation to the clinic. Expert Opin Biol Ther. 2024;24(11):1183–7. DOI: 10.1080/14712598.2024.2422358
  39. Peng BY, Dubey NK, Mishra VK, Tsai FC, Dubey R, Deng WP, et al. Addressing stem cell therapeutic approaches in the pathobiology of diabetes and its complications. J Diabetes Res. 2018;1:7806435. DOI: 10.1155/2018/7806435
  40. Wei L, Yan W, Shah W, Zhang Z, Wang M, Liu B, et al. Advancements and challenges in stem cell transplantation for regenerative medicine. Heliyon. 2024;10(16):e35836. DOI: 10.1016/j.heliyon.2024.e35836