In 2021, the first centenary of the discovery of insulin was commemorated, when Frederick Banting and Charles Best managed to isolate insulin from the pancreas of animals to treat a dog with diabetes, reducing its blood sugar levels in two hours.
It was the beginning of a new era in the management of diabetes, a disease that had been known for centuries and that until then had not found a truly effective treatment. The discovery of insulin marked a before and after in people with diabetes around the world, and without this advance, the current day-to-day life of these people would be very different.
diabetes. How?
The answer to this question may have been given by a study published in
«Nature Biotechnology» demonstrating, for the first time, that stem cells can form cells that closely mimic the structure and function of normal pancreatic islets.
It is about using pluripotent, embryonic or induced stem cells, with which to obtain pancreatic beta cells that in the future can be transformed into a treatment for patients with type 1 diabetes.
The researchers, including Diego Balboa, first author of the study and researcher at the
Center for Genomic Regulation (CRG), have transplanted stem cell-derived beta cells into mice and shown that they can effectively control glucose metabolism, “even better than pancreatic islets isolated from organ donors.”
Stem cell-derived pancreatic islet transplants they are no longer science fiction», recognizes ABC Salud Balboa. “Since 2014 there have been clinical trials in the US in which people with type 1 diabetes have been transplanted with these cells and there are currently several open clinical trials that are showing promising preliminary results».
For a long time, attempts have been made to produce functional beta cells from stem cells for use in transplants, which is gradually making it possible for this treatment to become a reality. However, beta cells produced from stem cells so far they have been immature, since they did not regulate insulin secretion well. This could explain why some of the clinical trials of these treatments with immature cells that have been carried out in the US have not made much progress.
What this group, led by Timo Otonkoski on the
University of Helsinki (Finland)is to optimize the functionality of pancreatic cells produced from stem cells.
This study describes the effective use of both embryonic stem cells, also called embryonic pluripotent stem cells, and which have been derived from embryos, and reprogrammed stem cells, also known as induced pluripotent stem cells, and which have been derived from skin or blood cells. “For practical purposes, both types of stem cells are equivalent and can be efficiently converted into functional pancreatic islets,” says the researcher at the
CRG.
Although we are early in the development of these therapies, there are important unknowns that clinical trials must resolve, Balboa says. Among the main challenges are determining what type of cells generate more effective transplants. “They are trying to transplant more immature cells, pancreatic progenitors, or more differentiated cells, functional pancreatic islets, similar to those described in our study.”
“Our work – he says – is an important advance to transform stem cells and convert them into spare parts to replace the destroyed or damaged beta cells of the pancreas, which are the cause of diabetes. While work remains to be done, these findings bring us one step closer to treating people with diabetes with stem cell-derived beta cells, something that no longer belongs in the realm of science fiction,” she says.
Another challenge is determining the transplant site, for example, subcutaneous, and how to transplant thes cells, free or within a device that encapsulates them and, in addition, there is a need for immunosuppressive drugs so that the recipients can tolerate these transplants.
To solve this need, he explains, “some companies are using modified stem cells that would be invisible to the recipient’s immune system and therefore tolerated without the need for immunosuppressive drugs.”
So can we talk about curing diabetes? Balboa comments on this advance in donor pancreatic islet transplantation in recent decades «has been shown to be a therapeutic option that would solve the dependence on insulin injections», but clarifies that «the problem is that these transplants are difficult to carry out, since they require the islets of more than one donor at a time and these donations are scarce and complex to process».
In his opinion, “the generation of pancreatic islets from stem cells will solve this shortage, since islets can be generated in an unlimited way in the laboratory, with adequate quality, safety and functionality controls.”
He already adds that the objective is that «this converts transplants of pancreatic islets derived from stem cells into a truly curative treatment, which works for a prolonged period of time, or even permanently. These findings are an important step towards this goal.”
On the other hand, the study of beta cell function published today is the most comprehensive in the field to date. In addition to insulin secretion, the scientific team investigated the functionality of systems that regulate insulin secretion, including metabolism and ion channels, and also connected the findings with gene expression in individual cells.
Diego Balboa indicates that islets derived from stem cells are also useful for studying the mechanisms of the pathology that underlies diabetes, work that he continues to develop in the
CRG: “We can generate millions of these cells in the laboratory and ask questions about what defects in genes and cellular machinery cause cells to fail, which helps us unravel the precise molecular causes of diabetes and identify new therapeutic targets. We also use the cells to explore the effects of new drugs to treat diabetes.”
“Our study will help further improve the production of islets from stem cells, which will facilitate their use in disease models and cell therapies,” he concludes. Timo Otonkoski.