Globally an estimated 422 million adults are living with diabetes according to 2016 data from the World Health Organisation (WHO).¹ Type 1 diabetes makes up approximately 10% of all cases and is one of the most common chronic diseases of childhood, affecting 1 in 500 children.
While the cause of type 1 diabetes is not fully understood, it is thought that the immune system plays an important role in causing damage to the beta-cells of the pancreas. Stem cells may offer a promising new approach in modulating the immune system to prevent or successfully treat diabetes.
Umbilical cord blood stem cells have particular characteristics that make them potentially useful for treating diseases based on restoration of peripheral immune tolerance. Cord blood contains a diverse mixture of cells that are not only capable of differentiation into other cell types, but is also considered immune tolerant due to a highly functional population of regulatory T cells. These regulatory T cells may play an important role in resetting the immune system imbalance in several auto-immune diseases.
To date no studies have shown that stem cells can prevent type 1 diabetes in humans, but cord blood has been shown to prevent and also cure type 1 diabetes in mice. The first study using cord blood to treat type 1 diabetic children was performed by Dr Michael Haller at the University of Florida. Autologous cord blood infusions were performed within 6 months of the diabetes diagnosis. The study demonstrated that the cord blood infusions were safe but only successfully increased the number of regulatory T cells in the short term (the effect lasted for 6-9 months) and provided some slowing of the loss of endogenous insulin. It was postulated that after diagnosis, too many beta cells have been destroyed and that preventative strategies may be more successful.²
Professor Maria Craig, a paediatric endocrinologist at the University of Sydney and Sydney Children’s Hospital Network is leading a pioneering five-year study. The Cord blood Reinfusion in Diabetes (CoRD) trial in Australia seeks to prevent the development of type 1 diabetes in high risk children. The primary hypothesis is that the infusion of autologous cord blood will restore immune tolerance in children with islet auto-immunity and delay or prevent progression to type 1 diabetes. The study is being funded by a grant from Australia’s largest private cord blood bank, Cellcare. Children aged 1-12 years, will be infused with their own stored cord blood and to qualify must have a close relative with type 1 diabetes and have tested positive for > two diabetes auto-antibodies (Insulin, GAD,IA2 and ZnT8 auto-antibodies).³
Another important study by Dr Piotr Trzonkowski at the University of Gdansk in Poland harvested regulatory T cells from diabetic children, multiplied them by culture and reinfused them. The study showed benefit compared to the control group as the children who received the infusion continued to make insulin.⁴
Cord blood from donors has also been tried in a novel concept called Stem Cell Educator therapy. Dr Yong Zhao form the University of Illinois conducted a study treating type 1 diabetic adults. The leucocytes of diabetic patients were passed through filters holding cord blood stem cells from public cord blood donors. The cells were mingled in the filter for 2 to 3 hours and the “re-educated” cells were returned to the patients. The patients exhibited improved diabetes control, requiring less insulin and had higher levels of regulatory T cells.⁵
Additionally ongoing research investigating mesenchymal stem cells to generate insulin producing pancreatic beta-cells in vitro, would provide an extraordinary cell source for drug discovery as well as cell transplantation therapy in diabetes. Previously insulin producing cells generated from pluripotent stem cells lacked many functional characteristics of endogenous beta-cells. Protocols are in development to generate hundreds of millions of these cells in vitro that will hopefully lead to successful transplantation.⁶
These trials and advances have broadened our understanding of the immune-modulatory properties of MSC’s and cord blood and will hopefully translate into effective cell- based therapies in the future.
- World Health Organization, Global Report on Diabetes. Geneva, 2016.
- Autologous umbilical cord blood infusion for type 1 diabetes. Haller, M.J et al. Experimental Hematology. 2008 (http://dx.doi.org/ 10.1016/j.exphem.2008.01.009)
- Cord Reinfusion in Diabetes Pilot Study- A pilot study to assess the feasibility of reinfusion of cord blood in children at risk of type 1 diabetes. https://www.anzctr.org.au Trial ID ACTRN12613000186752
- Clinical applications of Regulatory T-cells in Type 1 Diabetes. Marek-Trzonkowska et al. Pediatric Diabetes. 2013. 322-332 DOI: 10.1111/pedi.12029
- Reversal of Type 1 Diabetes via Islet β Cell Regeneration Following Immune Modulation by Cord Blood-Derived Multipotent Stem Cells. Zhao, Y et al. BMC Medicine 2012.10:3 DOI: 10.1186/1741-7015-10-3. ClinicalTrials.gov number: NCT01350219
- Generation of Functional Human Pancreatic β Cells In Vitro. Pagliuca F.W et al. Cell 2014. 428-439 (http://dx.doi.org/10.1016/j.cell.2014.09.040)