Rice pursues endgame for type 1 diabetes

A new 'sense and respond' technology could see to it that people living with type 1 diabetes can 'forget about it' - meet the researcher whose clear goal is to solve the complex management of diabetes for patients once and for all.

The new research was awarded a $US2.8 million grant to create hydrogel-encapsulated cells that, when placed into a patient, sense blood glucose levels and produce insulin on demand.

The encapsulated cell factories "fly under the radar" of the immune system to avoid detection and rejection, protecting and supporting their pancreatic islet cells.


William Marsh Rice University bioengineer Omid Veiseh (an inventor of 20 pending or awarded patents) ultimately wants patients with Type 1 diabetes to forget about it.


That's the goal his lab has declared with funding support from the US National Institutes of Health.


The agency has awarded Veiseh's lab a prestigious four-year, $2.8 million grant to design hydrogel-encapsulated cells that, when placed into a patient, sense blood glucose levels and produce insulin on demand.


Rice University Bioengineer Omid Veiseh

Rice University bioengineer Omid Veiseh, left, with graduate student Siavash Parkhideh, is leading an effort to develop gel-encapsulated cells for patients with diabetes that monitor blood glucose and release insulin when needed. Photo by Jeff Fitlow


These on-board drug factories would eliminate the need for patients to persistently monitor their blood glucose and administer insulin shots.


"Our hope is that one day patients can be insulin-independent and not have to think about diabetes," said Veiseh, an assistant professor of bioengineering who joined Rice in 2017.


"We want to get to the point where they get the treatment and live their lives normally."


Type 1 diabetes is an autoimmune disease, where the body's own immune system inadvertently destroys the insulin-producing beta cells of the pancreas.


Replacing the beta cells with protection from the immune system is a potential cure for many patients afflicted with this condition, Veiseh said.


To that end, his lab at Rice's BioScience Research Collaborative is developing thousands of distinct hydrogel capsules that can protect and support pancreatic islet cells.


A major challenge is developing hydrogel formulations which can hide these cells from the host immune system.


The lab's solution involves the synthesis of 7,000 variations of hydrogels, each carrying islet cells and an individual bar code.


These will allow the lab to inject multiple types of hydrogels into a small number of mice for in vivo testing.  (In vivo tests are conducted in live organisms; in vitro experiments are conducted in test tubes and the like.)


"We can't do this in vitro, only in vivo, but it would take an army to test thousands of individual animals," Veiseh said.


Using the innovative bar coding technique, batches of different cell/capsule combinations can be implanted and those that survive the animal's immune system can be identified based on their bar codes.


The codes themselves represent a unique approach, he said.


Rather than physically marking each cell - hard to do in a jelly - or using chemical means that could induce an immune response, the researchers will encase surrogate cells along with the islet cells.


These surrogates are  human umbilical vein endothelial cells. Because they're culled from thousands of donated umbilical cords and have their donors' distinct genomes, they can be easily identified through next-generation sequencing.


That will let the lab drastically cut the amount of time it will take to test all of its variants.


"That's going to be the first pass, and it will allow us to whittle down those 7,000 formulations to a manageable number," Veiseh said.


"Once we discover new leads, we will test those more rigorously to evaluate their ability to house and protect islet cells, and the cells' ability to survive and correct blood glucose."


The capsules will also have to ward off fibrosis, the body's tendency to wall off invading cells by building scar tissue.

Rice Uni Sense And Respond Team


Members of Rice's Veiseh Lab include, from left: Siavash Parkhideh, Alen Trubelja, Samira Aghlara-Fotovat, Sudip Mukherjee, Omid Veiseh, Maria Ruocco, Christian Schreib and Michael Doerfert. Photo by Jeff Fitlow


Veiseh has been developing novel materials that enable cell-based therapies for close to a decade.


He's a co-founder of Sigilon Therapeutics, a biotech company working to commercialize this approach for treatment of various chronic diseases.


He noted the development of implantable, drug-making cells is one of this year's  10 "breakthrough" technologies listed by the World Economic Forum.


While some approaches require occasional or even frequent cell injections, Veiseh's clear goal is to solve the complex management of diabetes for patients once and for all.


"When I started my postdoctoral research (at the Massachusetts Institute of Technology), I had a misperception that diabetes was not that big of a problem because we have insulin. But when I realized the challenges people face, particularly children, I was really inspired," he said. "


My team and I are committed to making a transformative impact for patients."


How the technology works

  • Creates a new class of implantable cell-based technologies that will "fly under the radar" of the immune system to avoid detection and rejection.
  • Genetically engineered allogeneic human cells are encapsulated to deliver a precisely engineered cell factory into the body to "sense and respond" to a need for insulin.
  • Provides a unique, controllable and dose-adjustable approach to delivering protein therapeutics that do not trigger the immune system in the body.
  • Proprietary cells are engineered ex vivo to produce high levels of protein at a controlled rate without the risk of introducing a gene construct into a patient's own cells.
  • Allows for developing long term programmable implants that can be upgraded when required or removed if desirable to provide control.

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