Type 1 diabetes mellitus (T1DM) is an autoimmune disease that attacks pancreatic β-cells, leading to the destruction of insulitis-related islet β-cells. Islet β-cell transplantation has been proven as a curative measure in T1DM. However, a logarithmic increase in the global population with diabetes, limited donor supply, and the need for lifelong immunosuppression restrict the widespread use of β-cell transplantation. Numerous therapeutic approaches have been taken to search for substitutes of β-cells, among which stem cell transplantation is one of the most promising alternatives. Stem cells have demonstrated the potential efficacy to treat T1DM by reconstitution of immunotolerance and preservation of islet β-cell function in recent research. cGMP-grade stem cell products have been used in human clinical trials, showing that stem cell transplantation has beneficial effects on T1DM, with no obvious adverse reactions. To better achieve remission of T1DM by stem cell transplantation, in this work, we explain the progression of stem cell transplantation such as mesenchymal stem cells (MSCs), human embryonic stem cells (hESCs), and bone marrow hematopoietic stem cells (BM-HSCs) to restore the immunotolerance and preserve the islet β-cell function of T1DM in recent years.


meta-analysis of ten studies with 239 patients showed that, compared with baseline levels, significant changes were found in the HbA1c, FBG, PBG, F-CP, and insulin requirements of patients with DM after they received MSC therapy.

Some of the included studies that explored the usefulness of treatment with MSCs in patients with T2DM found a significant decrease in insulin requirements and an increase in C-peptides. Other studies have reported that autologous MSCs are effective in animals and patients with T1DM. These results are consistent with our findings, and they support MSC transplantation as an effective treatment for DM. In clinical practice, the FBG and the 2-h postprandial blood glucose are the criteria for the diagnosis of diabetes, as they reflect the function of the islet cells, although there are other influencing factors. The HbA1c level, which reflects blood glucose control for the past 8–12 weeks, is a measure of diabetes control. Our meta-analysis found that the baseline levels of FBG, PBG, and HbA1c dropped significantly after MSC therapy. The subgroup analysis found that the decrease in the FBG and PBG of participants with T1DM was more pronounced than the changes in those with T2DM; the level of HbA1c in the MSC-treated group with T1DM was lower than that of the participants in the control group after 12 months of follow-up. Hence, it was clear that MSCs had a therapeutic effect on blood glucose regulation in patients with DM, and the benefits for patients with T1DM were more pronounced.

Our meta-analysis showed an increase in the F-CP level in the MSC-treated group with T1DM, which was higher than that of the control group, and an increase in the F-CP level of the MSC-treated group with T2DM after 12 months. The F-CP level is an indicator of the insulin secretion function of pancreatic islet cells, and an increased level indicates increased insulin secretion. The increase in insulin secretion may be due to the expansion of insulin-secreting B cells, or the result of increased insulin secretion of the remaining B cells. Our results also found that 7 included studies reported a significant decrease in insulin requirements after MSC therapy, compared to baseline. Similar results were found in participants with T2DM at 3, 6, and 12 months of follow-up; however, due to limitations of the trial and lack of data, the changes in the insulin requirements of participants with T1DM at each of the follow-ups could not be calculated. In conclusion, the efficacy of MSCs in reducing insulin requirements was consistent among the included studies, and it was sustained at the end of most studies’ follow-ups. However, studies with complete data and longer follow-ups are needed. We found that MSCs are more beneficial in the treatment of T1DM than T2DM.

No significant difference was found in the HbA1c or FBG levels at the end of the follow-up between the MCS-treated group and the control group. Nor was a significant change found in the FBG level of the MSC-treated group with T2DM. The F-CP level was lower in the MSC-treated group with T2DM than it was in the control group. A possible explanation for these findings is that the sample size was small, which might have led to insufficient statistical power. In addition, the inclusion of non-randomized studies in the meta-analysis could have led to bias.

Despite encouraging results in pre-clinical studies, key issues that need to be considered before MSC-based therapies become a safe and effective option for clinical researches. The clinical efficacy of MSCs is related to cell source, treatment cycle, culture expansion protocol, passage number, timing and route of administration, dosage, donor characteristics, freshly prepared, or cryopreserved cells. At present, the clinical application cycle of MSCs is difficult to be unified, and there is no unified treatment principle in the world. There are great differences between the diagnosis and treatment for different hospitals and laboratories. They were based on a small number of trials and need confirmation in larger randomized trials.



  1. Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271–81.  

  2. Atkinson MA, Eisenbarth GS. Type I diabetes: new perspectives on disease pathogenesis and treatment. Lancet. 2001;358(9277):221–9.  

  3. International Diabetes Federation (IDF) IDF Diabetes Atlas 8th Edition. Available online: http://www.diabetesatlas.org/. Accessed 17 Oct 2020.

  4. Forst T, Guthrie R, Goldenberg R, Yee J, Vijapurkar U, Meininger G, et al. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on back-ground metformin and pioglitazone. Diabetes Obes Metab. 2014 May;16(5):467–77. 

  5. De-Fronzo RA, Eldor R, Abdul-Ghani M. Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes. Diabetes Care. 2013;36(Suppl 2):S127–38.

  6. Jennifer L. Larsen. Pancreas transplantation: indications and consequences. Endocr Rev. 2004;25(6):919–46.

  7. Domínguez-Bendala J, Lanzoni G, Inverardi L, Ricordi C. Concise review: mesenchymal stem cells for diabetes. Stem Cells Transl Med. 2012;1(1):59–63.

  8. Yagi H, Soto-Gutierrez A, Parekkadan B, Kitagawa Y, Tompkins RG, Kobayashi N, et al. Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplant. 2010;19(6):667–79. 

  9. Joyce N, Annett G, Wirthlin L, Olson S, Bauer G, Nolta JA. Mesenchymal stem cells for the treatment of neurodegenerative disease. Regen Med. 2010;5(6):933–46. 

  10. Sharma RR, Pollock K, Hubel A, McKenna D. Mesenchymal stem or stromal cells: a review of clinical applications and manufacturing practices. Transfusion. 2014;54(5):1418–37. 

  11. Ling WF, Zhang JA, Yuan ZR, Ren G, Zhang L, Chen X, et al. Mesenchymal stem cells use IDO to regulate immunity in tumor microenvironment. Cancer Res. 2014;74(5):1576–87.

  12. Gharibi T, Ahmadi M, Seyfizadeh N, Jadidi-Niaragh F, Yousefi M. Immunomodulatory characteristics of mesenchymal stem cells and their role in the treatment of multiple sclerosis. Cell Immunol. 2015;293(2):113–21. 

  13. Zanone MM, Favaro E, Miceli I, et al. Human mesenchymal stem cells modulate cellular immune response to islet antigen glutamic acid decarboxylase in type 1 diabetes. J Clin Endocrinol Metab. 2010;95(8):3788–97. 

  14. Wassef MA, Fouad H, Sabry D, Afifi N, Abbas AM, Mostafa W, et al. Therapeutic efficacy of differentiated versus undifferentiated mesenchymal stem cells in experimental type I diabetes in rat. Biochem Biophys Rep. 2016;5:468–75. 

  15. Vanikar AV, Dave SD, Thakkar UG, et al. Cotransplantation of adipose tissue-derived insulin-secreting mesenchymal stem cells and hematopoietic stem cells: a novel therapy for insulin-dependent diabetes mellitus. Stem Cells Int. 2010;2010:582382.

  16. Deng ZH, Xu HY, Zhang JY, Yang C, Jin L, Liu J, et al. Infusion of adiposederived mesenchymal stem cells inhibits skeletal muscle mitsugumin 53 elevation and thereby alleviates insulin resistance in type 2 diabetic rats. Mol Med Rep. 2018;17(6):8466–74.

  17. Gao LR, Zhang NK, Zhang Y, Chen Y, Wang L, Zhu Y, et al. Overexpression of apelin in Wharton’ jelly mesenchymal stem cell reverses insulin resistance and promotes pancreatic β cell proliferation in type 2 diabetic rats. Stem Cell Res Ther. 2018;9(1):339.  

  18. Bhansali S, Dutta P, Kumar V, Yadav MK, Jain A, Mudaliar S, 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):471–81. 

  19. Liu XB, Zheng P, Wang XD, Dai G, Cheng H, Zhang Z, et al. A preliminary evaluation of efficacy and safety of Wharton’s jelly mesenchymal stem cell transplantation in patients with type 2 diabetes mellitus. Stem Cell Res Ther. 2014;5(2):57.

  20. Wan X, Wang WQ, Liu JM, et al. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;19(14):135.

  21. Luo DH, Wan X, Liu JM, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2018;27(6):1785–805.  

  22. DerSimonian R, Laird N. Meta-analysis in clinical trials revisited. Contemp Clin Trials. 2015;45(Pt A):139–45.

  23. Carlsson P-O, Schwarcz E, Korsgren O, le Blanc K. Preserved β-cell function in type 1 diabetes by mesenchymal stromal cells. Diabetes. 2015;64(2):587–92.  

  24. Zhang X, Xu L, Zhou YH, et al. Safety and efficacy of allogeneic amniotic mesenchymal stem cells transplantation in the treatment of primary type 1 diabetes mellitus. Shandong Med J. 2016;56(29):44–6.

  25. Yu WL, Gao H, Yu XL, et al. Umbilical cord mesenchymal stem cells transplantation for newly-onset type 1 diabetes. J Clin Rehabilitative Tissue Eng Res. 2011;15(23):4363–6.

  26. Hu JX, Yu XL, Wang ZC, Wang F, Wang L, Gao H, et al. Long term effects of the implantation of Wharton’s jelly-derived mesenchymal stem cells from the umbilical cord for newly-onset type 1 diabetes mellitus. Endocr J. 2013;60(3):347–57. 

  27. Guan LX, Guan H, Li HB, et al. Therapeutic efficacy of umbilical cord-derived mesenchymal stem cells in patients with type 2 diabetes. Exp Ther Med. 2015;9(5):1623–30.  

  28. Kong DX, Zhuang XH, Wang DQ, Qu H, Jiang Y, Li X, et al. Umbilical cord mesenchymal stem cell transfusion ameliorated hyperglycemia in patients with type 2 diabetes mellitus. Clin Lab. 2014;60(12):1969–76.  

  29. Hu JX, Wang YG, Gong HM, Yu C, Guo C, Wang F, 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):1857–66. 

  30. Jiang RH, Han ZB, Zhuo GS, Qu X, Li X, Wang X, et al. Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study. Front Med. 2011;5(1):94–100. 

  31. Tsai P-J, Wang H-S, Shyr Y-M, Weng Z-C, Tai L-C, Shyu J-F, et al. Transplantation of insulin-producing cells from umbilical cord mesenchymal stem cells for the treatment of streptozotocin-induced diabetic rats. J Biomed Sci. 2012;19(1):47.

  32. Hosokawa Y, Hanafusa T, Imagawa A. Pathogenesis of fulminant type 1 diabetes: genes, viruses and the immune mechanism, and usefulness of patient-derived induced pluripotent stem cells for future research. J Diabetes Investig. 2019;10(5):1158–64.  

  33. Skyler JS, Fonseca VA, Segal KR, et al. Allogeneic mesenchymal precursor cells in type 2 diabetes: a randomized, placebo-controlled, dose-escalation safety and tolerability pilot study. Diabetes Care. 2015;38(9):1742–9.


MSCs can improve the blood glucose control of patients with DM and can be used to treat DM safely and effectively in the short term, especially T1DM. However, the detection of long-term effects requires longer follow-up periods, larger sample sizes, and more trials. Furthermore, no serious adverse events or significant hypoglycemic episodes were observed in MSC-treated patients with DM in all 10 studies. Therefore, MSC transplantation is considered to be a safe treatment for DM.

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    It is a long established fact that a reader will be distracted by the readable content of a page when looking at its layout.