Israeli Startup Wants to Cure Diabetes by Making Micro-pancreases. It Worked on Mice

Never mind better insulin shots or cell implants for diabetics: Betalin Therapeutics has a unique approach

Ruth Schuster
Ruth Schuster
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These are "mice," not "rats," as zoological purists would know, even if nobody else cares.
These are "mice," not "rats," as zoological purists would know, even if nobody else cares.Credit:
Ruth Schuster
Ruth Schuster

A young Israeli company that has cured type-1 diabetes in mice and hopes to do the same for humans one day has won the MIXiii Biomed 2017 pharma startup competition, beating dozens of other firms.

Just how cured were these mice, exactly? "They were cured of advanced stages of severe diabetes," explains Prof. Eduardo Mitrani from the Hebrew University of Jerusalem, the father of this hopefully breakthrough technology, and head of the scientific advisory board at Betalin Therapeutics, named "the most innovative biopharma company of the year" at Biomed.

The diabetes in question is type-1, which is an autoimmune disease that destroys the pancreas' ability to secrete insulin, as well as severe cases of type-2. These conditions are chronic and need to be treated by insulin shots, for life.

Teams around the world are working on this not-uncommon disease, but the Israeli startup has a unique approach, says Mitrani, its scientific adviser.

Its secret is to treat diabetes not by aiming to transplant naked cells that secrete insulin, but by implanting, lab-built whole, albeit microscopic pancreata. "I think that, with some modesty, we're the only one trying to recreate the whole organ," he tells Haaretz.

Why create a whole micro-pancreas, with all the difficulty that entails, rather than just inject healthy naked pancreatic cells like everybody else?

Because that doesn't work. Transplanted cells die quickly. "It turns out that we are not built of cells but of tissues and organs," says Mitrani: A pancreatic cell does not and cannot operate in glorious isolation. It operates within the environment of the pancreas, which operates within the environment of the body, etc.

These micro-pancreases have been a great success in mice, as reported a year ago in PLOS ONE.

The testing technique for the technology involved chemically destroying the mice's insulin-producing cells, then implanting the micro-pancreata into the newly hyperglycemic rodents. (Being self-contained units, the micro-organs can be implanted virtually anywhere in the body.)

If the mouse lives, the micro-pancreas is working – it's controlling the animal's glucose levels. If the mouse dies, it isn't working.

Prof. Eduardo MitraniCredit: Alexander Elman

"We found we could keep the mice functioning even for three months, the longest period tested," says the professor, elaborating that without a working pancreas, we (and mice) cannot survive for more than a few days at most.

As a control for the experiment, they took mice that had survived all that for a month and removed the micro-pancreata, following which the animals died.

Ideally the team would have used pancreatic cells to create the micro-scaffolds on which they build their micro-organs, but they discovered that lung tissue worked better. For one thing, as Mitrani explained to Haaretz, 95% of the tissue in our pancreases is involved in producing digestive enzymes, not insulin regulation. For another, the lung tissue with its enormous surface area proved most compatible.

The engineered organs are made in the lab, and in contrast to say human ears grown on transgenic mice, these are microscopic.

Pressed on whether a microscopic micro-pancreas is enough to sustain a human, Mitrani explains simply: "You need a lot of them." Then he turns enthusiastic. "In fact, that's what make it so functional!" he told Haaretz. "Its very microscopic dimensions. By being so small, it doesn't need vascularization. It functions through diffusion, and will function anywhere in the body."

To elaborate the point: once implanted in the chemically-diabetic mice, the micro-pancreases do become vascularized, which means, they connect to our blood systems. That is, says Mitrani, simply what organs have evolved to do.

Theoretically, because it's so small, the micro-pancreas can survive without connecting to our blood systems. But actually that's how it monitors our blood glucose, and produces the correcting insulin.

When might this micro-pancreas technique be available for more than mice? Not for years, Mitrani confirms, and that's assuming they can raise the money for clinical trials, always a problem for biotechnology startups. Once they have the financing, they need to do broader animal testing, then human testing, which would be done either in Canada or the United States.

"The most successful marriage in evolution is between cells and their supporting connective tissue. Nature has been looking at it for 500 million years," says the professor. "We are unique because we are trying to preserve and reproduce this interaction."



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