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Matt Winkler
Matt Winkler
Articles (101) 

New Diabetes Research for Off-the-Shelf Cell Transplants Shows Promise

Researchers at Georgia Tech found a way to bypass rejection of pancreatic cell transplants by encasing them in a hydrogel shield. Could this challenge the future of insulin injections?

June 13, 2018 | About:

Another potential challenge to global diabetes giants Novo Nordisk (NYSE:NVO), Sanofi (NASDAQ:SNY) and Eli Lilly (NYSE:LLY) just took shape last week. The publication of new findings in the journal Nature suggest that insulin-producing islet cells can indeed be transplanted off-the-shelf – and without immunosuppression.

Consider: Annual diabetes costs in the U.S. amounted to $327 billion in 2017 according to the American Diabetes Association, a 26% increase in five years. It’s spiraling out of control, and for one main reason. Diabetes can only be managed. It cannot be cured. However, these new findings suggest that it may actually be possible to cure the disease outright.

That means a one-time treatment could eventually, in theory, replace a lifetime of insulin injections. Talk about cost savings.

How does it work?

Scientists from Georgia Tech have confirmed that islet cell transplantation together with what they call a hydrogel successfully engrafts allogeneic cells in mice without immunosuppressive drugs. The cells have survived for 200 days so far and researchers believe they can stretch that further, potentially indefinitely.

Various news reports are describing the hydrogel as “training” the immune system not to attack the islets, but this description is not entirely accurate. It can be more accurately described as a protective shield or barbed wire. Each gel particle is about 150 nanometers in diameter, about the same size as each islet cell. They surround each transplanted cell and present a ligand, a type of protein receptor that all cells broadcast on their membranes. This ligand, called FasL, normally activates apoptosis, or cell suicide, in T-effector cells. These are the immune cells that are chiefly responsible for organ rejection in allogeneic (different gene) transplants.

If a T-cell gets too close to the new islet cells then, it hits the ligand shield and essentially kills itself. In other words, the transplanted cells are encased in a protective layer of spikes like a porcupine. The immune system continues to function as normal for everything else in the body.

The researchers were able to simply mix islet cells from cadavers with the hydrogel and inject them into the fat pad of mice without any genetic matching. In humans, they believe it would be possible to inject the cells into the omentum, a layer of tissue that connects the stomach with the rest of the digestive system. They believe the omentum is the best target because it’s full of blood vessels for the islet cells to attach to.

Right now the researchers are putting their focus towards type I diabetes, a much smaller market than type II, probably because type I is an autoimmune disease, and protecting islet cells from the immune system as this treatment intends would negate the entire cause of the disease, increasing the chances of a full cure for type I. In type II, islet cells die gradually and spontaneously. This doesn’t mean the treatment wouldn’t work on type II, but rather that it’s slightly less clear due to causal factors if it would work long term.

In addition to challenging the diabetes market leaders, this new off-the-shelf approach challenges smaller companies working on diabetes stem cell therapies like Mesoblast (NASDAQ:MESO). Not only is this new approach simpler and cheaper, but stem cell therapies for islet replacement have been known to lead to tumors from errant stem cells.

This isn’t any kind of imminent threat to Novo, Sanofi or Eli Lilly of course, and all three have growing diabetes markets for the near to mid-term. But recent developments in the diabetes space looking to go beyond insulin injections paint the picture that the business models of these diabetes giants won’t last forever, and structural changes for these companies will eventually have to be made as medical technology advances. Together with advances like Oramed’s oral insulin candidate, now undergoing a phase II trial on 240 patients, the days of daily insulin injections may be numbered.

Disclosure: Long NVO.

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