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Synthetic Insulin-Producing Cells Designed, Tested

Diabetes items

(Centers for Disease Control and Prevention)

9 December 2016. Synthetic beta cells, like natural cells in the pancreas, were shown in tests with lab mice to sense glucose levels in the blood and produce insulin. A team from the lab of bioengineering professor Martin Fussenegger at ETH, the Swiss Federal Institute of Technology in Zurich, reported its finding in today’s issue of the journal Science (paid subscription required).

Glucose control and insulin levels are vital issues to people with diabetes, a chronic condition where the pancreas does not create enough insulin to process glucose that flows into the blood stream and cells for energy in the body. Type 1 diabetes is an autoimmune condition where the body is tricked into producing little or no insulin. Type 2 diabetes is a disorder where the pancreas produces some, but not enough insulin, or the body cannot process insulin, and accounts for some 90 percent of all diabetes cases. According to the International Diabetes Federation, diabetes affects 415 million people worldwide, of which 44 million are in North America.

People with diabetes need to continually monitor their blood glucose levels and provide insulin externally, usually through injections. Failure to adequately control blood glucose levels can lead to serious health consequences, including cardiovascular disorders, kidney failure, and tissue damage that can be life-threatening. The widespread and growing need for diabetes treatments or management led to many therapeutic strategies, including regenerating beta cells, the cells in the pancreas that respond to blood glucose levels and produce insulin.

Fussenegger’s lab is one of many research groups working on solutions for diabetes, which recently focused on transformation and culturing of adult stem cells from fat tissue into beta cells. The researchers found this approach slow and expensive, however, and in their new work are seeking a more direct and predictable process. This process, say the authors, should produce synthetic cells that both sense glucose levels and respond with sufficient insulin, and can help people with either type 1 or type 2 diabetes.

The team enlisted the aid of computational biology colleague Jörg Stelling that developed a computer model to predict the behavior of their synthetic cells as they modified or added components, which could then be verified experimentally.

The researchers began with a line of human embryonic kidney or HEK cells, a well-researched type of cell, where the cell membranes already have proteins that transport glucose, and potassium channels that respond to glucose levels. Fussenegger and colleagues then modified the HEK cells adding a calcium channel, where the calcium triggers the cells’ signaling mechanisms, and genes expressing insulin and glucagon-like peptide, or GLP-1 that helps regulate glucose levels in the blood.

The cells were designed to send glucose from the blood stream through their natural transport mechanisms into the interior, where potassium channels would close if glucose levels exceeded a specified level. Closing the potassium channels alters the voltage distribution in the cell membranes, which opens the calcium channels, sending signals to the genetically-altered mechanisms producing insulin and GLP-1.

The team tested the synthetic beta cells in lab cultures and mice induced with type 1 or type 2 diabetes. In mice with type 1 diabetes, the implanted beta cells stopped persistent high blood glucose levels. And in mice with type 2 diabetes, the synthetic cells improved internal insulin production and glucose tolerance. In both cases, the cells kept working for about 3 weeks.

The tests, the authors note, are only a proof of concept and the synthetic beta cells still need considerably more R&D, including human clinical trials, before they’re ready for the market. Nonetheless, ETH Zurich applied for patents on the technology with Fussenegger and first author Mingqi Xie listed as inventors.

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