Stem-cell implant prototypes pave the way towards life-long treatment for type 1 diabetes – ZME Science

New research is paving the way towards reliable, long-term treatments for type 1 diabetes. The work focused on developing implants based on stem cells that can deliver insulin directly into the bloodstream of diabetes patients.

While the implants are not yet ready for use in a clinical role, the research does prove the viability of such systems for use in the future. The implants consist of pancreatic endoderm cells derived from human pluripotent stem cells (PSCs) and were tested with 26 patients. After more research and development, once such implants become able to secrete levels of insulin that will have a clinical effect on their recipients, they could become a viable alternative to current insulin-delivery systems and islet replacement therapies (pancreatic transplants).

The device is band-aid sized and designed to contain the lab grown islet cells for subcutaneous implant. It allows the cells within to become vascularized to permit delivery of oxygen and nutrients and release of insulin into the bloodstream. It is also readily retrievable, said Dr. Timothy J. Kieffer of the University of British Columbia, corresponding author of the study, for ZME Science.

The team aims to provide an unlimited supply of insulin-producing cells for patients with type 1 diabetes, to mediate continuous, long-term treatment options while minimizing the invasiveness of the procedure.

Insulin is a hormone that keeps the levels of glucose (sugar) in our blood under control, and is produced by pancreatic -cells. Type 1 diabetes is characterized by the destruction of these cells and leads to dangerously high levels of glucose building up in patients bloodstreams. Current treatments for this condition involve the administration of insulin directly into the bloodstream, either via manual injection or through automated systems that a patient can wear, which deliver the hormone periodically. Another possibility although seen much more rarely in the grand scheme of things is to treat the condition through islet transplant from donor organs.

Each of these treatment options comes with its own drawbacks. Direct injections require users to monitor their own state, remember to perform the procedure, and also carry the risk that they administer the shots imperfectly. Automated devices can be very burdensome to wear for long periods of time, are associated with long-term complications, and can malfunction. Transplants are very intrusive procedures and the supply of donor organs is very limited compared to the demand.

As such, an alternative is required, the team argues.

The current study reports on a phase I/II clinical trial involving the use of pancreatic endoderm cells as one such alternative. The teams devices contain such cells in special capsules that allow for direct vascularization of the cells; these were implanted under the skin of the patients. The procedure did, however, run the risk of the participants bodies rejecting the implants, and thus involved an immunosuppressive treatment regimen that is commonly used in donor islet transplantation procedures. Possible side-effects of such treatments is an increased risk of cancer and infections in patients, as a direct consequence of their immune systems being suppressed.

That being said, the authors report that the devices worked as intended, and the cells within them started secreting insulin and delivering it directly into the participants bloodstreams in response to the glucose levels in their blood. Insulin expression (secretion) was recorded in 63% of the devices after they were explanted at time periods between 3 and 12 months after implantation. Insulin-secreting cells started accumulating progressively in these devices over a period of between 6 and 9 months after implantation.

Although not yet able to cover their full requirements for insulin, over a one-year study period, they reduced the amount of insulin participants needed to be administered by 20%. They also spent 13% more time in the target blood glucose range compared to pre-study periods.

We found the implants were able to produce insulin in a meal regulated manner like normal healthy pancreatic islets, albeit at low levels, Dr. Kieffer adds for ZME Science. The sponsor company ViaCyte recently reported achieving clinically meaningful levels of insulin when more of these devices were implanted (8) that resulted in a dramatic reduction in the insulin injection requirements accompanied by vastly improved control of blood sugar.

Overall, these devices were well-tolerated by their bodies and there were no severe adverse effects caused by the grafts. Two participants did experience serious adverse effects related to the immunosuppression treatment. Most of the adverse effects reported by participants, however, were related to the actual implantation/explantation surgeries, or to side-effects of the immunosuppressive treatment. All things considered, the team explains, the risk of local infection posed by the devices was very low, suggesting that the devices themselves are well-tolerated even in participants with a poor immune or healing response.

This does raise questions regarding the use of such devices over a patients whole life. An ideal solution to this would be an option to perform stem cell-based islet replacement therapy without the devices themselves, as this would bypass the need for immunosuppressive treatments altogether.

One of the major limitations of the study was the lack of a control group, so the findings should not be used to draw any conclusion on how effective such devices would be at treating type 1 diabetes. However, the study does show that they are relatively safe to use and validate the working principle behind their design. More research will be needed to determine the quantity of cells such implants should contain in order to produce clinically-relevant benefits for patients.

It was very exciting to see clear meal regulated insulin production in patients following the implants and also see islet cells in the retrieved devices that looked like normal healthy pancreatic islet cells. We now have clear proof of principle data that this stem cell-based approach can work, Dr. Kieffer adds for ZME Science.

Currently, the cells survive an average of 59 weeks after implantation. The total percentage of insulin-positive cells they contained at maturation was below the teams ideal target, however. The researchers are now working on solutions to promote vascularization between the grafts and the patients bodies, and on measures to improve the survival of the cells they contain.

Our ultimate goal is to entirely free patients from the burden of glucose monitoring and insulin injections, and without the use of any immunosuppression, Dr. Kieffer concluded in his email for ZME Science. We are thus very excited by the recent ViaCyte / CRISPR Therapeutics announcement that Health Canada has approved clinical testing of genetically modified cells that have been engineered to evade detection by the immune system.

With protocol refinements and immune-evasive cells, we hope to reach this goal.

The paper Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes has been published in the journal Cell Stem Cell.

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Stem-cell implant prototypes pave the way towards life-long treatment for type 1 diabetes - ZME Science