UCSF researchers develop novel technique to generate functional, insulin-producing beta-like cells

Hebrok Lab

Members of the Hebrok lab at the Diabetes Center at UCSF contributed to a novel study that will open new possibilities for treating type 1 and type 2 diabetes. Pictured from left are: Holger Russ, Audrey Parent, Jennifer Ringler, Thomas Hennings, Gopika Nair, Sapna Puri, and Matthias Hebrok.

UCSF researchers develop novel technique to generate functional, insulin-producing beta-like cells

Findings open widespread possibilities to treating diabetes

BY KATHLEEN JAY

Diabetes Center at UCSF

SAN FRANCISCO (April 24, 2015) -- Yesterday, researchers in the Hebrok lab at the Diabetes Center at UCSF published a study that identifies a novel technique for transforming human embryonic stem cells into insulin-producing cells.

Opening a wide range of possibilities for treating both type 1 and type 2 diabetes, the study -- entitled "Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro" -- was published in The EMBO Journal.

"Cell therapies that utilize functional insulin-producing beta cells produced from human stem cells hold great promise for the treatment of diabetes," Matthias Hebrok, PhD, and Director of the Diabetes Center at UCSF, said. "Researchers from the Diabetes Center are now able to generate 'beta-like' cells that are very similar to human beta cells."

"In terms of developing cell therapies for treating diabetes, this novel technique will allow us to study beta cell function under defined cell culture conditions, as well as conduct screens to evaluate the efficacy of known and new drugs meant to improve function," Hebrok added.

The UCSF team -- which is led by Hebrok lab members Holger Russ, Audrey Parent, Jennifer Ringler, Thomas Hennings, Gopika Nair, Sapna Puri and Matthias Hebrok -- developed the technique using human embryonic stem cells.

"In a lab setting, we demonstrated how current pancreatic differentiation protocols induce precocious endocrine differentiation," Russ, a post-doctoral fellow and lead author on the paper, said. "This leads to the formation of undesired polyhormonal endocrine cells."

"We then established a simplified, large-scale suspension culture-based differentiation system. In doing so, we were able to make the correct temporal specification of subsequent progenitors, resulting in the generation of glucose-responsive beta-like cells in vitro," Russ added.

"This approach not only permits us to rapidly generate a reproducible supply of functional human beta-like cells, but also enables us to make detailed investigations into human pancreas development and beta cell biology," Russ said.

Beta-like cells -- which exhibit key features that are similar to mature insulin-producing human beta cells -- remain functional after short-term transplantation, as well as reduce blood glucose levels in diabetic mice, Russ added.

Diabetes Center researchers will continue to fine-tune their research to focus on identifying alternative sources for creating insulin-producing cells from human embryonic stem cells.

"We are already working on the next generation of beta-like cells that look even better with regard to functionality and efficiency," Hebrok added.

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Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro

Holger A Russ1, Audrey V Parent1, Jennifer J Ringler1, Thomas G Hennings1, Gopika G Nair1,

Mayya Shveygert2, Tingxia Guo1,†, Sapna Puri1, Leena Haataja3, Vincenzo Cirulli4, Robert Blelloch2,

Greg L Szot1, Peter Arvan3 & Matthias Hebrok1,*

DOI 10.15252/embj.201591058 | Published online 23.04.2015

The EMBO Journal (2015) embj.201591058