Time to cure type 1 diabetes: Danish researchers among the leaders

Disease and treatment 10. jan 2018 2 min Adjunkt Jacqueline Ameri Written by Morten Busch

People with type 1 diabetes strongly depend on injecting synthetically produced insulin. However, this situation may change within a few years. Today, researchers can already recreate insulin-producing beta cells from stem cells, which can be implanted in people with diabetes. The researchers have not yet streamlined stem cell production, and they still need to ensure that the body does not destroy the new beta cells again. A Danish research group hopes to be the first to achieve this if they can get funding.

Globally, more than 36 million people suffer from type 1 diabetes, a lifelong condition that requires daily insulin injections. The immune system of people with the disease destroys the insulin-producing beta cells in the pancreas. Three years ago, researchers in the United States developed a method of producing sufficient stem cells to re-establish insulin production in the body. Danish researchers were right behind them and have now taken a further leap towards achieving this goal.

“The key challenge within stem cell therapy for type 1 diabetes has been to find biomarkers that differentiate between the various stem cell derivatives generated during maturation in the culture dish. We have now found a unique protein – a marker called GP2 [glycoprotein 2] – that is expressed on the surface of the pancreatic progenitor cells that can mature into the insulin-producing cells. The purification of these cells at an early stage enables us to generate a safer and more efficacious end product,” explains Jacqueline Ameri, Assistant Professor, Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, University of Copenhagen.

Better techniques than others

The challenge of developing and differentiating stem cells intended to become insulin-producing beta cells in the pancreas is to ensure that the cells are exposed to specific signalling chemicals called factors so they can develop in a specific direction. If a stem cell initially develops in the wrong direction, it will end up fulfilling a function other than producing insulin.

“If stem cells that are not fully differentiated are placed in the patients, they may do more harm than good. The stem cells that are introduced must therefore be at exactly the right stage, and we must ensure that they will not develop in a wrong direction. The surface marker GP2 is essential in arriving at a uniform stem cell population that develops into beta cells.”

The researchers have searched intensely to find a marker that is only present on the progenitor cells that can mature and result in the insulin-producing beta cells.

“Starting with a purified population of progenitors to beta cells instead of immature stem cells not only eliminates the risk of getting unwanted and potentially cancer-causing cells but also makes the next stage much simpler, because developing and maturing progenitor cells into fully mature beta cells makes the final step easier, more reproducible and less expensive.”

Avoiding attacks by the immune system

This simpler process has proved to be a major advantage for the future advances of the Danish researchers. Differentiating stem cells is very expensive. The research group therefore already decided some years ago to establish a spin-out company, PanCryos. This can ensure that the new knowledge is converted into actual treatment and that they can raise sufficient funds for manufacturing the final cell product and initiating the clinical trials that need to be carried out to realize the treatment.

“Although PanCryos is among the few research groups in the world that are the most advanced in diabetes, cell therapy is a complex and expensive field for conducting clinical work and still in its infancy, and unfortunately less high risk-willing biotech venture capital is available in Europe compared with the United States, making it more challenging for a Danish start-up company to compete globally.”

Jacqueline Ameri, co-founder and CEO of PanCryos, is therefore looking for funding to carry out a Phase 1 clinical trial in the near future. Even though the stem cell treatment works in the laboratory and in mice, researchers know only too well that getting the treatment to work in humans will be much more challenging.

“The biggest hurdle is clearly to ensure that the body does not attack and destroy the newly implanted stem cells, because that will put us back where we started. Although some of our competitors have attempted to insert cells using small capsules that can be implanted and then removed again, we believe that the key to overcoming the final obstacle is immunotherapy, which gets the immune system to leave the new beta cells alone.”

Efficient generation of glucose-responsive beta cells from isolated GP2+ human pancreatic progenitors” has been published in Cell Reports. Jacqueline Ameri and several co-authors are employed at the Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, University of Copenhagen.

The aim of our work is to produce GMP certified stem cell derived beta cells to initiate a phase 1 trial aiming to assess the safety of hPSC-derived b...

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