Stem cells as a potential therapeutic option for type 1 diabetes

A person being measured for their blood sugar levels

As researchers investigate new treatments for type 1 diabetes, newborn stem cells show promise as a possible therapeutic option.¹ Years of pre-clinical research and clinical trials suggest a potential role for newborn stem cells in treating this challenging disease. By preserving their own newborn cells, CBR^® client families may have access to future novel therapies for serious diseases including type 1 diabetes.

Type 1 diabetes and the need for new treatment options

Together, type 1 and type 2 diabetes affect around 9% of the global population.² Individuals with type 1 diabetes do not produce sufficient amounts of insulin, a hormone produced by the pancreas which removes sugar from the bloodstream and into cells, thus regulating the body’s blood sugar levels. Type 1 diabetes has no cure, and management of this autoimmune disease involves regulating blood sugar levels to prevent complications including cardiovascular disease, diabetic neuropathy, diabetic retinopathy, kidney damage, and issues during pregnancy.³ The standard therapy for type 1 diabetes involves exogenous insulin administration,⁴ although this treatment presents challenges in maintaining proper glucose levels and comes with a risk of hypoglycemia.^3,4 With the need for better therapies for this chronic metabolic disorder, researchers are looking to cellular therapy as a new treatment option, and the use of stem cells shows promise as a novel mechanism for treating type 1 diabetes.⁵

Newborn stem cells as a therapeutic option for type 1 diabetes

Newborn stem cells include both hematopoietic stem cells (HSCs) from umbilical cord blood and mesenchymal stem cells (MSCs) from cord tissue, and each of these cell types has unique regenerative properties that are of interest for targeting type 1 diabetes. These cells are collected after birth in a non-invasive manner without ethical objections^6,7 and can be cryogenically preserved for later use.^8,9,10 Relative to adult sources of stem cells, newborn stem cells are highly proliferative and more pristine than adult stem cells, allowing for greater flexibility in donor-recipient matching potential.^11,12,13

HSCs are being researched for their potential use in both transplant and regenerative medicine to treat type 1 diabetes. In transplant medicine, HSCs have attracted research interest for their potential role in resetting the patient’s immune system and impeding the autoimmune destruction of pancreatic beta cells.¹⁴ A 2012 publication demonstrated that in 13 patients with new onset of type 1 diabetes, an autologous stem cell transplant using HSCs from peripheral blood led to decreased insulin dependence.¹⁵ In regenerative medicine, HSCs have been found to aid in the generation of regulatory T cells, which are regulators of peripheral immune tolerance and their insufficiency can lead to type 1 diabetes.¹⁶ While research investigating the use of HSCs, including those from cord blood, as a potential treatment for type 1 diabetes is promising,¹⁷ more studies are needed to determine whether this cell type may be effective as a therapeutic option.

MSCs have numerous qualities that suggest a potential role in treating the sequelae of type 1 diabetes, including paracrine signaling, immunomodulation, anti-inflammation, apoptosis inhibition, and angiogenesis.^1,18 Pre-clinical research using MSCs to explore potential routes of disease treatment has revealed many promising mechanisms, including:

Anti-inflammation: MSCs have been shown to reduce kidney inflammation which can lead to improvement in kidney damage.¹⁹
Anti-fibrosis: MSCs are capable of inhibit the certain signaling pathways, thereby reducing glomerular fibrosis.²⁰
Anti-oxidative stress: Administration of MSCs has resulted in reduction in reactive oxidative species, which are molecules involved in the promotion of diabetes.²¹
Apoptosis inhibition: MSCs are able to reduce the rate of renal cell apoptosis and regulate apoptosis-related proteins.^22,23

Multiple studies have reported that umbilical cord-derived MSCs can preserve endogenous β-cell function in adults with recent-onset type 1 diabetes which may slow disease progression and reduce long-term complications of the disease. ^24,25

The future of newborn stem cells in research for type 1 diabetes

Despite promising evidence that stem cells hold potential for treating type 1 diabetes, more research is needed to determine whether cellular therapy will provide a much-needed option for treating this serious autoimmune condition. In the coming years, research is expected to focus on optimizing factors such as cell dose, time of treatment, and method of injection of MSCs.²⁶

Preservation of newborn stem cells with CBR, a leader in the field of newborn stem cell preservation, may one day present families with a potential resource for future clinical trials or novel treatments for type 1 diabetes.

1. Moreira, A., Kahlenberg, S. & Hornsby, P. Therapeutic potential of mesenchymal stem cells for diabetes. J. Mol. Endocrinol. 59, R109–R120 (2017). 2. Saeedi, P. et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res. Clin. Pract. 157, 107843 (2019). 3. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010 Jan;33 Suppl 1(Suppl 1):S62-9. doi: 10.2337/dc10-S062. Erratum in: Diabetes Care. 2010 Apr;33(4):e57. PMID: 20042775; PMCID: PMC2797383. 4. Warshauer, J. T., Bluestone, J. A. & Anderson, M. S. Review New Frontiers in the Treatment of Type 1 Diabetes. Cell Metab. 31, 46–61 (2019). 5. Kakkar, A. et al. Current Status of Stem Cell Treatment for Type I Diabetes Mellitus. Tissue Eng. Regen. Med. 15, 699–709 (2018). 6. Maslova, O., Novak, M. & Kruzliak, P. Umbilical Cord Tissue-Derived Cells as Therapeutic Agents. 2015, (2015). 7. Deus, I. A., Mano, J. F. & Custódio, C. A. Perinatal tissues and cells in tissue engineering and regenerative medicine. Acta Biomater. 110, 1–14 (2020). 8. Troyer, D. L. & Weiss, M. L. Wharton’s jelly-derived cells are a primitive stromal cell population. Stem Cells 26, 591–599 (2008). 9. Afonso Cornélio, D. & Batistuzzo de Medeiros, S. R. Genetic evaluation of mesenchymal stem cells. Rev. Bras. Hematol. Hemoter. 36, 238–240 (2014). 10. Lansdorp, P. M., Dragowska, W. & Mayani, H. Ontogeny-related changes in proliferative potential of human hematopoietic cells. J. Exp. Med. 178, 787–791 (1993). 11. Ballen, K. Update on umbilical cord blood transplantation. F1000Research 6, 1556 (2017). 12. Gragert, L. et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N. Engl. J. Med. 371, 339–348 (2014). 13. Bárcia, R. N. et al. What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells? Stem Cells Int. 2015, 583984 (2015). 14. Ben Nasr, M. et al. The use of hematopoietic stem cells in autoimmune diseases. Regen. Med. 11, 395–405 (2016). 15. Li, L. et al. Autologous hematopoietic stem cell transplantation modulates immunocompetent cells and improves β-cell function in Chinese patients with new onset of type 1 diabetes. J. Clin. Endocrinol. Metab. 97, 1729–1736 (2012). 16. Visperas A, Vignali DA. Are Regulatory T Cells Defective in Type 1 Diabetes and Can We Fix Them? J Immunol. 2016 Nov 15;197(10):3762-3770. doi: 10.4049/jimmunol.1601118. PMID: 27815439; PMCID: PMC5119643. 17. Stiner R., Alexander M., Liu G., et al. Transplantation of stem cells from umbilical cord blood as therapy for type 1 diabetes. Cell Tissue Res. Nov;378(2):155-162(2019). 18. Pixley, J. S. Mesenchymal stem cells to treat type 1 diabetes. Biochim. Biophys. Acta - Mol. Basis Dis. 1866, 165315 (2020). 19. Li, Y. et al. Early intervention with mesenchymal stem cells prevents nephropathy in diabetic rats by ameliorating the inflammatory microenvironment. Int J Mol Med 41, 2629–2639 (2018). 20. Lv, S. et al. Mesenchymal stem cells ameliorate diabetic glomerular fibrosis in vivo and in vitro by inhibiting TGF-β signalling via secretion of bone morphogenetic protein 7. Diabetes Vasc. Dis. Res. 11, 251–261 (2014). 21. Ezquer, F. et al. Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in Mice with Severe Diabetes Mellitus. Biomed Res. Int. 2015, 164703 (2015). 22. Nie, P. et al. Human umbilical cord mesenchymal stem cells reduce oxidative damage and apoptosis in diabetic nephropathy by activating Nrf2. Stem Cell Res. Ther. 12, 450 (2021). 23. Chen, L. et al. Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorate Nephrocyte Injury and Proteinuria in a Diabetic Nephropathy Rat Model. J. Diabetes Res. 2020, 8035853 (2020). 24. Hu J, Yu X, Wang Z, 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.60(3):347–357(2013). 25. Carlsson P., Espes D., Sisay S., et al. Umbilical cord-derived mesenchymal stromal cells preserve endogenous insulin production in type 1 diabetes: a Phase I/II randomized double-blind placebo-controlled trial. Diabetologica. Aug;66(8):1431-1441 (2023). 26. Zhu, Y. et al. Administration of mesenchymal stem cells in diabetic kidney disease: mechanisms, signaling pathways, and preclinical evidence. Mol. Cell. Biochem. (2022) doi:10.1007/s11010-022-04421-4.