Human regulatory T cells (Tregs), a type of white blood cell and part of our body’s immune system, are showing promising results as a potential therapeutic option for Type 1 diabetes and other autoimmune diseases.

Building on previous work, University of Florida Health Researchers, in collaboration with investigators at the University of California, San Francisco School of Medicine, published results from a recent study demonstrating that Tregs can be isolated from cryopreserved cord blood and expanded in the laboratory under a good manufacturing practice (GMP) compliant setting, suggesting the cells could be used in patients with Type 1 diabetes¹. Researchers are excited about the findings as it suggests that cord blood may be a suitable source for this potential therapeutic approach in regenerative medicine.

What is Type 1 diabetes?

Type 1 diabetes, commonly referred to as juvenile diabetes, is a life-threatening chronic condition in which the pancreas produces little to no insulin, which is needed to regulate our bodies’ blood sugar levels. In patients with Type 1 diabetes, a group of cells in the immune system, called T effector cells, attacks the insulin-producing cells of the pancreas. Insulin is a hormone made by certain cells of the pancreas, allowing glucose to enter cells and helps regulate our blood sugar. Because the body’s own cells are attacked by the immune system, Type 1 diabetes is defined as an autoimmune disease.

How is Type 1 diabetes managed today?

Insulin therapy either given by injections or a pump that connects to a part of the body by catheter is needed daily. It is challenging for Type 1 diabetics to regulate how much insulin they need based on fluctuating factors throughout the day, such as what food was eaten, how much exercise or stress was involved that day, and other health problems that may be occurring. If a person takes too much insulin, the body burns too much glucose that results in dangerously low blood sugar levels called hypoglycemia. If a person takes too little insulin, it results in dangerously high levels called hyperglycemia. Most diabetics must check their blood glucose levels regularly throughout the day and adjust their target insulin intake accordingly.

One interesting approach to treating the underlying cause of Type 1 diabetes being explored in clinical trials is trying to restore the balance that normally exists between the T effector cells and T regulatory cells, a part of the immune system responsible for, as the name implies, regulating other cells in the immune system.

Several groups have hypothesized, and are testing the safety and feasibility² of, isolating and expanding Tregs from an individual’s peripheral blood and then administering the purified cells back into the person through an IV. One downside of this approach though, especially in the setting of pediatric patients, is that it requires a substantial blood draw or leukapheresis. This is where using cryopreserved cord blood as an alternative, and very practical, starting material could be more beneficial.

Could Tregs from cord blood be a new potential treatment option?

Cord blood contains many types of cells, including Treg cells, the subject of this study. Previous research efforts have shown it is safe to perform an infusion of one’s own cord blood in patients with Type 1 diabetes^{3, 4}. In this new study from the University of Florida Health Researchers, researchers demonstrated that the Treg cells in both fresh and previously cryopreserved cord blood could be effectively isolated and expanded under Good Manufacturing Practice (GMP) compliant conditions¹. In other words, the final product met all the criteria appropriate for administration into human patients. As a next step, the goal will be to attempt to slow down the body’s attack on cells and replace them with healthy cells. In addition to demonstrating that the expanded Tregs from cryopreserved cord blood were comparable to Tregs from peripheral blood, the authors report several features of the cord blood-derived Tregs that may translate to additional benefits for treating autoimmune conditions such as Type 1 diabetes¹. These exciting results open the door to exploring the safety and efficacy of administering expanded Tregs from one’s own cryopreserved cord blood for patients with Type 1 diabetes.

This research was funded by grants from multiple organizations seeking to advance treatment options for Type 1 diabetes. In addition to sponsoring a grant, we are proud to have several members of CBR’s scientific and medical team as contributors to the study manuscript.

Sources:

1. Seay HR et al. Expansion of Human Tregs from Cryopreserved Umbilical Cord Blood for GMP-Compliant Autologous Adoptive Cell Transfer Therapy. 2017. Mol Ther Methods Clin Dev. 2016 Dec 24;4:178-191.
2. Bluestone JA et al. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci Translational Medicine. 2015 Nov 25;7(315):315ra189.
3. Haller, M.J. et al. Autologous umbilical cord blood transfusion in young children with type 1 diabetes fails to preserve C-peptide. 2011 Diabetes Care 34, 2567–2569.
4. Haller, M.J. et al. Autologous umbilical cord blood infusion followed by oral docosahexaenoic acid and vitamin D supplementation for C-peptide preservation in children with Type 1 diabetes. 2013. Biol. Blood Marrow Transplant. 19, 1126–1129.