In  a medical milestone, researchers have implanted pancreatic cells from a deceased donor into a person with type 1 diabetes. These cells have produced insulin for months without the need for the recipient to be given immunosuppressant drugs, thanks to genetic modifications made with the CRISPR system.

This represents the possibility of a cure for this autoimmune disease that affects millions of people who undergo constant insulin injections. The Seattle-based firm Sana Biotechnology conducted the study, and Aaron Kowalski, executive director of Breakthrough T1D, a leading global organization for type 1 diabetes (T1D) research and advocacy, commented, “The preliminary data have certainly encouraged our community, and it’s a really elegant approach.”

Ultimately, the aim is to make genetic modifications to stem cells to evade the immune system and subsequently direct their development towards insulin-secreting cells, since previously these types of unedited cells  had already demonstrated their effectiveness.

On the other hand, independent research groups have failed to corroborate Sana’s claim that the immune system can be evaded in a study involving only one person who received a low dose of cells for a short period. This is insufficient to prevent insulin dependence. Therefore, its clinical efficacy has not been demonstrated, according to Tim Kieffer, a molecular endocrinologist at the University of British Columbia in Vancouver, Canada.

However, for Kieffer, who was the scientific director of the biotechnology company ViaCyte, dedicated to the development of cell therapies for type 1 diabetes, immune concealment seems “convincing” and “an important milestone towards the goal of effective cell therapy without chronic immunosuppression.”

As is known, insulin administration could currently be avoided in people with type 1 diabetes by transplanting islet cells from a deceased donor. This system allows for the restoration of insulin production for several years. However, this alternative is not commonly used due to a shortage of pancreas donors, as well as because it requires permanent immunosuppression, which carries side effects and the risk of cancer and infection.

To overcome the shortage of donors, some companies have used stem cell techniques to obtain pancreatic islets in the laboratory in unlimited quantities. The company Vertex obtained pancreatic cells from embryonic stem cells and transferred them to 12 patients with type 1 diabetes. After one year, these patients no longer required insulin injections, and the company plans to seek approval for this treatment soon. Meanwhile, Reprogenix Bioscience in Hangzhou, China, is producing islets of Langerhans from reprogrammed stem cells derived from the recipient’s own adipose tissue. In both cases, the treatment requires the administration of immunosuppressants, either to protect the donor cells from attack by the immune system or to mitigate the autoimmune attack that can even target the patient’s own cells.

The study conducted by Sana aims to avoid the use of immunosuppressant drugs. To achieve this, they used pancreatic islet donations from a person without diabetes and deactivated two genes using the CRISPR system. This prevented T cells from recognizing the islet cells as foreign. Furthermore, using a virus, they achieved the expression of the CD47 protein, which protects them from natural killer cells. After injecting approximately 80 million edited cells into a person with type 1 diabetes (a low dose for safety), they found that cells lacking some of the genetic modifications were eliminated by the immune system. In contrast, those carrying all the changes remained unaffected, secreting insulin for 12 weeks without immune intervention. Follow-up reports indicate that this protection has continued for six months. Sonja Schrepfer, Sana’s scientific founder and a transplant immunologist currently at Cedars-Sinai Medical Center in Los Angeles, California, and co-director of the study, says that these cells “truly overcome the transplant barrier.”

In a recent issue of the  New England Journal of Medicine, Kevan Herold,  an immunologist at Yale School of Medicine in New Haven, Connecticut, states that we are witnessing the first milestones of a treatment that type 1 diabetes patients have long desired. It would be truly unique, available to anyone who needs it to restore insulin production without the need for immunosuppressants or needles. The genetic modification that protects the immune system, combined with obtaining pancreatic beta cells from stem cells, will produce the best results, he asserts.

Both Vertex and Sana are pursuing this approach and plan to conduct clinical trials next year. However, their proposed CD47-based hiding technique to prevent  natural killer  cell attacks has faced criticism, as several independent groups have  struggled to replicate the purported protection. “Many of us have tried and failed,” says Deepta Bhattacharya, an immunologist at the University of Arizona in Tucson. He adds, “If they actually start curing people with type 1 diabetes, then I’ll shut up and say, ‘Mea culpa.’” 

Using stem cells to obtain pancreatic islets would be excellent and would provide us with a virtually inexhaustible source. As we have seen, we can use embryonic stem cells or stem cells reprogrammed from other tissues in our body.

From an ethical standpoint, it would be better to use reprogrammed cells. This avoids the use and destruction of the human embryo, which, as has been conclusively proven by biology, is a genuine living being that only needs to continue its development to reach adulthood and, therefore, deserves our utmost respect from the very first moment of its existence.