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 recipient needing immunosuppressive drugs, thanks to genetic modifications made using the CRISPR system.

This represents the possibility of a cure for this autoimmune disease that affects millions of people who are constantly on insulin injections. The Seattle, Washington-based firm Sana Biotechnology conducted the study, and Aaron Kowalski, executive director of Breakthrough T1D, a leading global organization in type 1 diabetes (T1D) research and advocacy, commented: “The preliminary data have certainly encouraged our community, and it’s a truly 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 these types of unedited cells had previously demonstrated their effectiveness.

On the other hand, independent research groups have failed to corroborate Sana’s claim that it can evade the immune system. This study included only one person who received a low dose of cells over a short period of time: this is not enough 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 chief scientific officer of the biotechnology company ViaCyte, which is developing cell therapies for type 1 diabetes, immune concealment seems “convincing” and “an important milestone toward 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 cadaveric islet cells. This system can restore insulin production for several years. However, this alternative is not often used due to a lack of pancreas donors and because it requires permanent immunosuppression, which brings with it side effects and the risk of cancer and infection.

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

The study conducted by Sana aims to avoid the use of immunosuppressive drugs. To do so, they used a donation of pancreatic islets from a person who did not suffer from the disease and deactivated two genes using the CRISPR system. This way, the T cells did not identify 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 (which represents a low dose for safety reasons), they found that the cells that lacked any of the genetic modifications were eliminated by the immune system. In contrast, those with all the changes remained unharmed, secreting insulin for 12 weeks without any action by the immune system. Follow-up reports confirm that this protection has continued for six months. Sonja Schrepfer, Sana’s scientific founder and transplant immunologist currently at Cedars-Sinai Medical Center in Los Angeles, California, who co-led the study, says these cells “really overcome the transplant barrier.”

In a recent issue of the New England Journal of Medicine, Kevan Herold, an immunologist at the 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 always desired. It would be something 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 route and plan to conduct clinical trials next year. However, their proposed CD47-based cloaking technique to avoid natural killer cell attacks has received criticism, as several independent groups have struggled to replicate the purported protection. “Many of us have tried it and failed,” says Deepta Bhattacharya, an immunologist at the University of Arizona in Tucson. At the same time, she declares, “If they actually start curing people with type 1 diabetes, then I’ll just shut up and say, ‘Mea culpa’”.

Using stem cells to obtain pancreatic islets would be excellent and would allow us to have a practically 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 resort to the use of reprogrammed cells. This avoids the use and destruction of the human embryo, which, as biological science has conclusively proven, is a genuine living being that only needs to continue its development to reach adulthood and, therefore, deserves our full respect from the first moment of its existence.