Encapsulated Stem Cells to Treat Diabetes

A research group from the Sanford-Burnham Medical Research Institute in La Jolla, San Diego, California has used pluripotent stem cells to make insulin-secreting pancreatic beta cells that are encapsulated in a porous capsule from which they secrete insulin in response to rising blood glucose levels.

“Our study critically evaluates some of the potential pitfalls of using stem cells to treat insulin-dependent diabetes,” said Pamela Itkin-Ansari, an adjunct assistant professor with a joint appointment at UC San Diego. “We have shown that encapsulated hESC-derived pancreatic cells are able to produce insulin in response to elevated glucose without an increase in the mass or their escape from the capsule. This means that the encapsulated cells are both fully functional and retrievable.”

For this particular study, Itkin-Ansari and her colleagues used glowing cells to ensure that their encapsulated cells stayed in the capsule. To encapsulate the cells, this group utilized a pouch-like encapsulation device made by TheraCyte, Inc. that features a bilaminar polytetrafluoroethylene (PTFE) membrane system. This pouch surrounds the cells and protects from the immune system of the host while giving cells access to nutrients and oxygen.

With respect to the cells, making insulin-secreting beta cells from embryonic stem cell lines have met with formidable challenges. Not only are beta cells differentiated from embryonic stem cells poorly functional, but upon transplantation, they tend to be fragile and poorly viable.

To circumvent this problem, encapsulation technology was tapped to protect donor cells from the ravages of the host immune system. However, an additional advance made by Itkin-Ansari and her colleagues is that when they encapsulated islet-precursor cells, derived from embryonic stem cells, these cells survived and differentiated into pancreatic beta cells. In fact, islet progenitor cells turn out to be the ideal cell type for encapsulation, since they are heartier, and differentiate into beta cells quite efficiently when encapsulated.

In their animal model tests, these cells remained encapsulated for up to 150 days. Also, as an added bonus, because the progenitor cells develop glucose responsiveness without significant changes in mass, they do not outgrow their capsules.

In order to properly get this protocol to work in humans, Itkin-Ansari and her group has to scale up the size of their capsules and the number of cells packaged into them. Another nagging question is, “How long will an implanted capsule last in a human patient?

“Given the goals and continued successful results, I expect to see the technology become a treatment option for patients with insulin-dependent diabetes,” said Itkin-Ansari.

To date, Itkin-Ansari and others have been able to successfully treat diabetic mice. The problem with these experiments is that they mice were made diabetic by treatment with a drug called beta-alloxan, which destroys the pancreatic beta cells. Human type 1 diabetic patients have an immune system that is sensitized to beta cells. Even though the encapsulation shields the beta cells from contact with the immune system, will this last in human patients with an aggressive immune response against their own beta cells? It seems to me that induced pluripotent cells made from the patient’s own cells would be a better choice in this case than an embryonic stem cell line.

Nevertheless, this is a fine piece of research for diabetic patients.

Umbilical Cord Stem Cells Normalize Blood Glucose Levels in Diabetic Mice

Diabetes mellitus results from an insufficiency of insulin (Type 1 diabetes) or an inability to properly respond to insulin (Type 2 diabetes). Type 1 diabetes is caused by an attack by the patient’s own immune system on their pancreatic beta cells, which synthesize and secrete insulin. It is a disease characterized by inflammation in the pancreas. This suggests that abatement of inflammation in the pancreas might provide relief and delay the onset of diabetes.

Mesenchymal stem cells isolated from umbilical cord connective tissue, which is also known as Wharton’s jelly (WJ-MSCs), have the ability to reverse inflammatory destruction and might provide a way to delay or even reverse the onset of Type 1 diabetes.

To test this possibility, Jianxia Hu, Yangang Wang, and their colleagues took 60 non-obese diabetic mice and divided them into four groups: a normal control group, a normal diabetic group, a WJ-MSCs prevention group that was treated with WJ-MSCs before the onset of diabetes, and a WJ-MSCs treatment group that was treated with WJ-MSCs after the onset of diabetes.

After their respective treatments, the onset time of diabetes, levels of fasting plasma glucose (FPG), fed blood glucose levels and C-peptide (an indication of the amount of insulin synthesized), regulation of cytokines, and islet cells were examined and evaluated.

After WJ-MSCs infusion, fasting and fed blood glucose levels in WJ-MSCs treatment group decreased to normal levels in 6-8 days and were maintained for 6 weeks. The levels of fasting C-peptide of the WJ-MSC-treated mice was higher compared to diabetic control mice. In the WJ-MSCs prevention group, WJ-MSCs protected mice from the onset of diabetes for 8-weeks, and the fasting C-peptide in this group was higher compared to the other two diabetic groups.

Other comparisons between the WJ-MSC-treated group and the diabetic control group, showed that levels of regulatory T-cells (that down-regulate autoinflammation), were high and levels of pro-inflammatory molecules such as IL-2, IFN-γ, and TNF-α. The degree of inflammation in the pancreas was also examined, and pancreatic inflammation was depressed, especially in the WJ-MSCs prevention group.

These experiments show that infusions of WJ-MSCs can down-regulate autoimmunity and facilitate the recovery of islet β-cells whether given before or after onset of Type 1 Diabetes Mellitus. THis suggests that WJ-MSCs might be an effective treatment for Type 1 Diabetes Mellitus.

See March 2014 edition of the journal Endocrine.