Co-culturing Immune Cells with Umbilical Cord Stem Cells Reverses Type 1 Diabetes in a Small Study

Type 1 diabetes results from an inability to make sufficient quantities of insulin. Insulin is made by specific cells in the pancreatic islets (also known as the islet of Langerhans). Most type 1 diabetics have suffered destruction of their pancreatic beta cells. Beta cell destruction can result from physical trauma to the pancreas, which causes the digestive enzymes of the pancreas to destroy the beta cells. For example, pancreatitis, pancreatic surgery, or certain industrial chemicals can cause diabetes. Also, particular drugs can also cause temporary diabetes, such as corticosteroids, beta blockers, and phenytoin. Rare genetic disorders (Klinefelter syndrome, Huntington’s chorea, Wolfram syndrome, leprechaunism, Rabson-Mendenhall syndrome, lipoatrophic diabetes, and others) and hormonal disorders (acromegaly, Cushing syndrome, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma) also increase the risk for diabetes.

Additionally, viral infections of pancreas can cause the immune response to destroy pancreatic cells, and this wipes out enough beta cells to cause the onset of type 1 diabetes. The coxsackievirus family of viruses is a family of enteric viruses that are cause infections that are sometimes associated with the onset of type 1 diabetes, as are mumps and congenital rubella. In most cases, genetic factors cause the immune system to view the pancreatic beta cells as foreign invaders, and the beta cells are attacked and destroyed. Researchers have found at least 18 genetic loci that are designated IDDM1 – IDDM18 that are related to type 1 diabetes. The IDDM1 region contains the “HLA genes” that encode proteins called “major histocompatibility complex”. HLA genes encode cell-surface proteins that act as “bar codes” for the immune system. When cells have the proper bar codes on their cell surfaces, the immune system recognizes those cells as being a part of the body in which they reside, and the immune system leaves them alone. Any cells that do not have the right bar codes are attacked and destroyed, which is known as the “graft versus host response.” Therefore, it is fair to say that HLA genes affect the immune response. New advances in genetic research are identifying other genetic components of type 1 diabetes. Other chromosomes and genes continue to be identified.

A recent paper attempts to cure type 1 diabetes by using umbilical cord stem cells. Umbilical cord stem cells (UCSCs) have the ability to greatly calm down the immune system. UCSCs secrete a wide variety of molecules that prevent immune cells from reacting to and destroying other cells, and also have many cell surface proteins that bind to the surfaces of immune cells and put them to sleep (see Abdi et al., Diabetes 2008;57:1759-67 & Aguayo-Mazzucato C. and Bonner-Weir S, Nature Reviews Endocrinology 2010;6:726-36).

Animal experiments have shown that co-culturing UCSCs with circulating immune cells alters the immune response against pancreatic beta cells and greatly increases the ability of the animal to regulate blood glucose levels (Zhao et al., PLoS ONE 2009;4:e4226). The UCSCs seem to “re-educate” the immune cells so that they do not recognize the pancreatic islets are foreign anymore. Therefore, Yong Zhao and his colleagues in Theodore Mazzone’s laboratory at the University of Chicago, IL, and collaborators at the General Hospital of Jinan Military Command, Shandong, China, used human UCSCs to re-educate immune cells in human type 1 diabetic patients.  See here for this paper.

To do this, they circulated the blood of each patient through a close-loop system that separated the immune cells (lymphocytes) from whole blood. Thee lymphocytes were then co-cultured with UCSCs for 2-3 hours and then returned to the patients.

The results were remarkable. Six patients in group A, who all had some residual beta cell function showed successively improved insulin production 12-24 weeks after treatment. They also showed a reduced need for insulin shots, and overall improvement of their fasting blood glucose levels. Six patients in group B, who had no residual beta cell function, showed increased production of insulin production 12 week after treatment. This is an incredible finding because those without beta cells essentially grew new ones that were not attacked by the immune system. The group B group also saw successively reduced requirements for injected insulin. The patients in the control, whose immune cells did not undergo re-education by UCSCs showed no improvement.

Furthermore, the patients whose immune cells were re-educated by the UCSCs, did not experience any adverse effects. This procedure seems to be quite safe and feasible.

There is a word of caution here. These patients must be followed over several years to establish that the re-education of the lymphocytes is maintained over time. Also, this study is quite small and despite the amazing results, a larger study is needed. All the same, this is an incredible result that reverses type 1 diabetes, and even though caution is needed, embryonic stem cells were not required to do this.

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Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).