Though it can be treated reasonably well, type 1 diabetes remains a serious condition that profoundly impacts the lives of millions of people globally. Once a death sentence, T1D is now a liveable chronic condition that requires regular injections of external insulin to maintain healthy blood sugar levels.

The discovery of insulin in the early 20th century represented a major advancement in the treatment of diabetes. Recently, researchers have announced exciting new breakthroughs in the field of stem cell research which may signal the next great advancement in the treatment of T1D. This time, however, they say they may have found a cure.

What is Type 1 Diabetes?

In healthy individuals, blood sugar sends signals to special cells to produce a hormone called insulin. These cells, called beta cells, normally exist in clusters (called islets) scattered throughout the pancreas. The insulin produced by these beta cells facilitates the metabolism of blood sugar, keeping its concentration in the bloodstream to safe levels.

Diabetes is characterized by the inability of the diabetic’s body to produce insulin. This leaves the body without a mechanism for regulating blood sugar, the effects of which can be catastrophic. Unchecked hyperglycaemia can lead to nerve damage, amputation, and in severe cases, death. Even with modern treatments, many diabetics face the probability of a significantly reduced lifespan.

Type 1 diabetes (T1D) is a subset of diabetes, where the inability to produce insulin results from a dysfunctional immune response. T1D individuals’ immune systems are hostile to the beta cells in their pancreas, errantly seeing them as foreign entities and mobilizing T cells to attack and destroy them. Wiping out these crucial beta cells destroys the body’s ability to produce insulin, leaving T1D individuals at perpetual risk of hyperglycaemia if not constantly monitored and treated.

Disadvantages of Current Treatment Protocols

Daily insulin injections have been the gold standard for treating diabetes since the discovery of insulin by Banting and Best in the 1920s. A century later, and in many ways little has changed. Significant improvements have been made to available insulin products, but the core fact of daily injections and constant monitoring remains a reality for diabetics.

In other words, medicine has improved its ability to treat diabetes, but curing the disease has remained an impossibility. But that may soon change, based on research that started when scientists discovered the potential that grafting beta cells offered for long -term insulin regulation in diabetics.

Grafting: A New Approach

In the 1970s, researchers began considering the possibility of transplanting beta cells from non-T1D cadavers into the bodies of T1D patients. The idea was that the beta cell implants, or grafts, would take up residence in the diabetic’s body and perform their normal function: releasing insulin into the bloodstream in response to high blood sugar levels.

Researchers initially found modest success with this technique in mice, but encountered two major issues when they attempted to replicate the procedure in human trials.

The first problem was that donor tissue was scarce, and only a small percentage of the available donor tissue would survive the transplanting process. This limited the feasibility of the procedure for a large-scale implementation.

The second, and perhaps more significant, problem was immune rejection. Ultimately, the recipients were still diabetics, and their immune systems were no less hostile to implanted beta cells than they had been toward the individuals’ native beta cells. Implants would be attacked and, in most cases, simply destroyed. This was prevented somewhat successfully by giving the patients immune-suppressing medications, and indeed this has become the standard protocol (known as the Edmonton protocol) for beta cell grafting. However, these medications come with the downside of needing to be taken perpetually, and they leave patients susceptible to infections and other complications.

The Edmonton protocol never gained widespread popularity for these reasons; however, it did serve the valuable role of proving that, if the obstacles could be tackled, such implants could effectively cure T1D and leave former diabetics with the long-term ability to produce their own supply of insulin internally.

The Limitless Potential of Stem Cells

Realizing the potential that beta cell grafts offered, researchers began searching for ways to address obstacles to this method.

The issue of limited beta cell supply was tackled first. Researchers had the idea of attempting to create their own supply of beta cells, rather than relying on harvesting them from cadavers. To do so, they experimented with a special kind of cell called a stem cell.

Stem cells are normal human cells that exist in everybody. But unlike skin cells or brain cells, which have a specific form and function, stem cells have no specific role. They are a sort of “blank slate”; a cell with the potential to become any other kind of cell within your body. This process of transforming from a generalized stem cell to a specialized cell is known as “differentiation”, and occurs naturally in your body.

Stem cells respond to chemical cues in their environment that let them know what kind of cell they should differentiate into. By figuring out which chemical cues tell stem cells to become beta cells, researchers would be able to induce stem cells into becoming beta cells in virtually unlimited quantities. The only limiting factor would be the availability of stem cells.

Formerly, stem cells were only available from human foetal tissue harvested from aborted pregnancies. This method was both controversial, and inherently limited the supply of stem cells to the availability of foetal tissue. A newer technique solves both issues by instead using stem cells derived from adult human tissue through a process involving various genes and other factors. These adult stem cells are known as induced pluripotent stem cells (iPS cells), and can be acquired in limitless quantities.

However, even iPS cells may become obsolete. Once researchers determine precisely which chemical cues induce stem cells to become beta cells, they will have successfully created a line of beta cells that will reproduce into self-sustaining generations of beta cells. Such propagation will create unlimited supplies of beta cells, solving one of the two major problems involved with beta cell grafting and bringing the scientific community that much closer to curing T1D.

Avoiding the immune response

The second challenge – preventing a destructive immune response toward grafts – remains more difficult to solve. Several lines of research are underway to solve this problem.

Encapsulation

One possible approach, broadly known as encapsulation, involves keeping the grafts physically partitioned from the body’s immune-responsive T cells. This is no easy feat, however; beta cells require excellent access to a person’s bloodstream in order to accurately monitor and match insulin secretion to blood sugar levels. Since T cells exist in the bloodstream, this presents an obvious challenge.

Various encapsulation methods are being tested, with mixed success. Attempts at encapsulation have fallen into one of two categories: macro or micro.

Macro-encapsulation involves surrounding a cluster of beta cells in a special packet designed to limit access to T cells. Such attempts have generally failed, since the recipients’ bodies either recognize the packet as foreign and reject it, or simply develop new blood vessels into the packet that carry T cells in the blood stream. Next generation macro-encapsulation will seek to use new material technologies that avoid these problems, though they are still undergoing clinical trials.

Micro-encapsulation takes a different approach, coating individual beta cell clusters, or “islets”, in an immune-repellant coating. These coated islets are then grafted inside a synthetic pouch that has been placed in the recipient’s body previously, avoiding much of the immune response and hopefully increasing acceptance rates of grafted tissue. These products are also still in various trial phases.

Biological engineering

Still, other researchers envision a more technical approach. Companies like ViaCyte have begun researching the prospect of engineering molecular changes to the beta cells themselves to make them invisible to the immune system.

This approach draws inspiration from similar processes in nature; for instance, foetal cells that carry specific cellular markers to indicate to the mother’s immune system that they should not be attacked, despite being “foreign”. By mimicking these features through bioengineering, it is possible to imagine a new-and-improved beta cell that evades detection by the body, and thus never requires immunosuppression drugs.

This approach too has downsides. Immune systems exist for a reason, and purposefully blinding a person’s immune system to a kind of cell within the body leaves the person vulnerable to any harmful effects those cells might have in the future. For instance, if an implanted beta cell mutated and spawned a line of cancerous cells, the body would have no chance of mounting a defense.

Researchers have already started working out how they might avoid such problems. Cells can be engineered to contain a kind of “self-destruct” button, which would cause only those cells to die off if a transplant recipient were to ingest a specific kind of trigger chemical. This would allow the patient and their physician to maintain control over the cell line, shutting them down in a worst-case scenario.

While a definitive cure for T1D has not yet been found or demonstrated, these lines of research show incredible promise for the prospect of eliminating a disease that has devastated countless lives. What’s important is that the concept of grafting has been shown to work, in theory, to give diabetics the ability to produce insulin. What remains to be seen is whether stem cells will fulfill their promise to yield a limitless supply of stem cells, and whether other techniques can prevent them from being destroyed once implanted.