Beta-cell therapies for type 1 diabetes: Transplants and bionics

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Xenotransplant: Can pig cells make up the shortage?

Use of animal kidneys (xenotransplant) is a potential solution to the shortage of human organs for transplant.

In theory, pigs could be a source. Porcine insulin is similar to human insulin (differing by only 1 amino acid), and it should be possible to breed “knockout” pigs that lack the antigens responsible for acute humoral rejection.21

On the other hand, transplant of porcine islets poses several immunologic, physiologic, ethical, legal, and infectious concerns. For example, porcine tissue could carry pig viruses, such as porcine endogenous retroviruses.21 And even if the pigs are genetically modified, patients will still require immunosuppressive therapy.

A review of 17 studies of pig islet xenotransplant into nonhuman primates found that in 5 of the studies (4 using diabetic primates) the grafts survived at least 3 months.22 Of these, 1 study used encapsulation, and the rest used intensive and toxic immunosuppression.

More research is needed to make xenotransplant a clinical option.

Transplanting stem cells or beta cells grown from stem cells

Stem cells provide an exciting potential alternative to the limited donor pool. During the past decade, several studies have shown success using human pluripotent stem cells (embryonic stem cells and human-induced pluripotent stem cells), mesenchymal stem cells isolated from adult tissues, and directly programmed somatic cells. Researchers have created stable cultures of pluripotent stem cells from embryonic stem cells, which could possibly be produced on a large scale and banked.23

Human pluripotent stem cells derived from pancreatic progenitors have been shown to mature into more functional, islet-like structures in vivo. They transform into subtypes of islet cells including alpha, beta, and delta cells, ghrelin-producing cells, and pancreatic polypeptide hormone-producing cells. This process takes 2 to 6 weeks. In mice, these cells have been shown to maintain glucose homeostasis.24 Phase 1 and 2 trials in humans are now being conducted.

Pagliuca et al25 generated functional human pancreatic beta cells in vitro from embryonic stem cells. Rezania et al24 reversed diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. The techniques used in these studies contributed to the success of a study by Vegas et al,26 who achieved successful long-term glycemic control in mice using polymer-encapsulated human stem cell-derived beta cells.

Reversal of autoimmunity is an important step that needs to be overcome in stem cell transplant for type 1 diabetes. Nikolic et al27 have achieved mixed allogeneic chimerism across major histocompatibility complex barriers with nonmyeloablative conditioning in advanced-diabetic nonobese diabetic mice. However, conditioning alone (ie, without bone marrow transplant) does not permit acceptance of allogeneic islets and does not reverse autoimmunity or allow islet regeneration.28 Adding allogeneic bone marrow transplant to conditioned nonobese diabetic mice leads to tolerance to the donor and reverses autoimmunity.


While we wait for advances in islet cell transplant, improved insulin pumps hold promise.

One such experimental device, the iLet (Beta Bionics, Boston, MA), designed by Damiano et al, consists of 2 infusion pumps (1 for insulin, 1 for glucagon) linked to a continuous glucose monitor via a smartphone app.

The monitor measures the glucose level every 5 minutes and transmits the information wirelessly to the phone app, which calculates the amount of insulin and glucagon required to stabilize the blood glucose: more insulin if too high, more glucagon if too low. The phone transmits this information to the pumps.

Dubbed the “bionic” pancreas, this closed-loop system frees patients from the tasks of measuring their glucose multiple times a day, calculating the appropriate dose, and giving multiple insulin injections.

The 2016 summer camp study29 followed 19 preteens wearing the bionic pancreas for 5 days. During this time, the patients had lower mean glucose levels and less hypoglycemia than during control periods. No episodes of severe hypoglycemia were recorded.

El-Khatib et al30 randomly assigned 43 patients to treatment with either the bihormonal bionic pancreas or usual care (a conventional insulin pump or a sensor-augmented insulin pump) for 11 days, followed by 11 days of the opposite treatment. All participants continued their normal activities. The bionic pancreas system was superior to the insulin pump in terms of the mean glucose concentration and mean time in the hypoglycemic range (P < .0001 for both results).

Bottom line

As the search continues for better solutions, advances in technology such as the bionic pancreas could provide a safer (ie, less hypoglycemic) and more successful alternative for insulin replacement in the near future.

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