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.