Diabetes treatment with umbilical cord stem cells

19/02/2024 Quản Trị

Diabetes, both type 1 and type 2, is highly prevalent worldwide. Many serious complications, which can be life-threatening, can arise from uncontrolled diabetes. The conventional approach to diabetes treatment includes injected insulin or oral anti-diabetic drugs, but they come with potential complications and can affect the patient’s health negatively. Therefore, clinicians strive to improve patient care with cell therapies using embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs). ESCs exhibit nearly unlimited plasticity, including differentiation into β-cells for insulin production, but they raise possible ethical concerns. With iPSCs, there is also a high risk of tumors that can inherit additional somatic mutations. MSCs can be a better choice to avoid both disadvantages above.

Treating diabetes with traditional methods

Patients with type 1 diabetes, an autoimmune disease, lose the ability to make insulin from pancreatic β cells and may require weekly or monthly insulin injections. β-cells play an important role in glucose homeostasis by sensing blood glucose and releasing insulin to maintain physiological glucose levels within a range that ensures biological interactions in the body [1]. Once the body loses these cells because of autoimmune destruction, type 1 diabetics will lose control of blood sugar levels, leading to hyperglycemia. With current improved insulin infusion therapies, certain effectiveness has been achieved. However, injecting exogenous insulin from outside into the body often has side effects compared to creating internal insulin from endogenous β cells. This insulin injection method is considered safer and has fewer complications than pancreas transplants, which are major surgery, leading to risks for patients [2]. Therefore, doctors rarely perform pancreas transplantation and often combine it with kidney transplantation in patients with type 1 diabetes and end-stage renal disease. Therefore, clinicians have devised a better method of creating insulin produced from β cells through stem cells, which can partly solve the problem of limited donor material sources for transplantation [3-5].

Stem cells in clinical trials for diabetes treatment

As we all know, human organs and tissues have the ability to restore their structure and function completely. However, some medical conditions restrict the body’s ability to self-recover. That is why researchers in regenerative medicine have studied the potential of stem cells to repair tissue and restore organ functions. Based on those principles and origins, researchers in regenerative medicine have utilized the diverse potential of embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs) to restore or maintain insulin secretion [6].

MSCs exhibit very low levels of immune responses. MSCs are considered clinically safe and have good tolerability [7]. Over 60 trials addressed 21 patients with type 1 and 2 diabetes, and from these trials, different humoral characteristics of MSCs addressed different disease aspects (CinicalTrials.gov). MSCs play a role in immune tolerance for type 1 diabetes patients, aiding in β-cell recovery or protection. Researchers employ the anti-inflammatory properties of MSCs in type 2 diabetes to address low-grade chronic inflammation, which is a key factor in insulin resistance and β-cell dysfunction. Sometimes, although MSCs do not cure the disease, studies have shown some positive aspects of partial blood sugar improvement [8,9].

However, to ensure the best transfer of stem cells during the proliferation culture process, controlling the problem of infection and infectious diseases is essential. The International Society for Cellular Therapy (ISCT) has identified MSCs as clinically defined by differentiation into (bone, cartilage, and fat) [10], in vitro proliferation, and expression. It is necessary to perform the expression of surface markers, such as CD73, CD90, and CD105.

Immunomodulatory properties of umbilical cord-derived MSCs

MSCs are currently the most studied cells in diabetes-related trials. By invasive methods, MSCs can be isolated from various tissues, usually from bone marrow and adipose tissue. However, collecting MSCs from cord blood and umbilical cords (considered commonly discarded medical waste) is non-invasive [11]. Umbilical cord blood and umbilical cord have become valuable medical products as we increasingly learn and research their applications in disease treatment. Stem cell therapy is one of the most promising and effective methods for treating diabetes because of its non-cancerous and less immunosuppressive properties. MSCs derived from the baby’s umbilical cord find extensive use in cell-based therapies for clinical applications. Among their various properties, immunomodulatory, regenerative, and proliferative abilities facilitate diabetes treatment partly by ameliorating hyperglycemia [12]. MSCs from umbilical cord blood have immunomodulatory effects on T lymphocytes, B lymphocytes, dendritic cells (DCs), and natural killer (NK) cells. Besides their immunomodulatory effects, several research reports have described that MSCs can be induced to differentiate into insulin-producing cells under defined conditions, generating ideal β-cells for traditional alternative therapy.

Potential for MSCs from cord blood and umbilical cord for diabetes

Umbilical cord blood-derived cells are an important biological resource for β-cell generation in diabetes therapy. Cord blood MSCs have similar characteristics to other MSC sources, including multiple immunomodulatory effects, differentiation potential, and adaptation into insulin-producing cells, providing advantages for cell growth for clinical application in treating diabetes. Many preclinical and clinical studies have showed the regenerative potential of MSCs from umbilical cord blood for treating diabetes and its associated secondary complications. MSCs from umbilical cord blood are believed to be much safer for clinical use as they do not show any side effects after transplantation, unlike iPSCs and ESCs.


  1. Perakakis, Nikolaos, and Christos S. Mantzoros. “Immune therapy in type 1 diabetes mellitus-Attempts to untie the Gordian knot?.” Metabolism-Clinical and Experimental65, no. 9 (2016): 1278-1285.
  2. Anazawa, T., Saito, T., Goto, M., Kenmochi, T., Uemoto, S., Itoh, T., Yasunami, Y., Kenjo, A., Kimura, T., Ise, K. and Tsuchiya, T., 2014, July. Long-term outcomes of clinical transplantation of pancreatic islets with uncontrolled donors after cardiac death: a multicenter experience in Japan. In Transplantation proceedings(Vol. 46, No. 6, pp. 1980-1984). Elsevier.
  3. Karnieli, Ohad, Yael Izhar-Prato, Shlomo Bulvik, and Shimon Efrat. “Generation of insulin-producing cells from human bone marrow mesenchymal stem cells by genetic manipulation.” Stem cells25, no. 11 (2007): 2837-2844.
  4. Madec, A. M., R. Mallone, G. Afonso, E. Abou Mrad, A. Mesnier, A. Eljaafari, and Charles Thivolet. “Mesenchymal stem cells protect NOD mice from diabetes by inducing regulatory T cells.” Diabetologia52, no. 7 (2009): 1391-1399.
  5. Fiorina, Paolo, Mollie Jurewicz, Andrea Augello, Andrea Vergani, Shirine Dada, Stefano La Rosa, Martin Selig et al. “Immunomodulatory function of bone marrow-derived mesenchymal stem cells in experimental autoimmune type 1 diabetes.” The Journal of Immunology183, no. 2 (2009): 993-1004.
  6. Moreira, Alvaro, Samuel Kahlenberg, and Peter Hornsby. “Therapeutic potential of mesenchymal stem cells for diabetes.” Journal of molecular endocrinology59, no. 3 (2017): R109-R120.
  7. Lalu, Manoj M., Lauralyn McIntyre, Christina Pugliese, and Duncan J. Stewart. “Safety of cell therapy with mesenchymal stromal cells (MSCs): a systematic review.”  CLINICAL TRIALS IN CRITICAL CARE(2010): A6043-A6043.
  8. Hu, Jianxia, Yangang Wang, Huimin Gong, Chundong Yu, Caihong Guo, Fang Wang, Shengli Yan, and Hongmei Xu. “Long term effect and safety of Wharton’s jelly-derived mesenchymal stem cells on type 2 diabetes.” Experimental and therapeutic medicine12, no. 3 (2016): 1857-1866.
  9. Guan, Li‑Xue, Hui Guan, Hai‑Bo Li, Cui‑Ai Ren, Lin Liu, Jin‑Jin Chu, and Long‑Jun Dai. “Therapeutic efficacy of umbilical cord-derived mesenchymal stem cells in patients with type 2 diabetes.” Experimental and Therapeutic Medicine9, no. 5 (2015): 1623-1630.
  10. Stiner, Rachel, Michael Alexander, Guangyang Liu, Wenbin Liao, Yongjun Liu, Jingxia Yu, Egest J. Pone, Weian Zhao, and Jonathan RT Lakey. “Transplantation of stem cells from umbilical cord blood as therapy for type I diabetes.” Cell and tissue research378, no. 2 (2019): 155-162.
  11. Kim, Ju-Yeon, Hong Bae Jeon, Yoon Sun Yang, Wonil Oh, and Jong Wook Chang. “Application of human umbilical cord blood-derived mesenchymal stem cells in disease models.” World journal of stem cells2, no. 2 (2010): 34.
  12. Koblas, Tomas, S. Mitchell Harman, and Frantisek Saudek. “The application of umbilical cord blood cells in the treatment of diabetes mellitus.” The Review of Diabetic Studies2, no. 4 (2005): 228.