First successful reprogramming of liver cells to pancreas progenitor cells based on a single factor
It is now possible to reprogram cells from the liver into the precursor cells that give rise to the pancreas by altering the activity of a single gene. A team of researchers at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) has now accomplished this feat in mice. Their results should make it feasible to help diabetic patients through cell therapy.
This is a 3-D map of liver and pancreatic buds in a mouse embryo. Cells of the pancreas are marked in red and green, while liver cells appear in blue.
Image: Francesca Spagnoli, MDC
In patients suffering from type I diabetes, their immune system turns against their own bodies and destroys a type of pancreatic cell called islet cells. Without these cells, the pancreas is unable to produce the hormone insulin and blood glucose rises, which leads to diabetic disease. At that point, such patients need to inject insulin for the rest of their lives.
A way to provide a lasting help to the afflicted may be to grow new pancreatic cells outside of the body. MDC group leader and researcher Dr. Francesca has been pursuing the idea of reprogramming liver cells to become pancreatic cells. Dr. Spagnoli's team has now succeeded in thrusting liver cells into an "identity crisis" -- in other words, to reprogram them to take on a less specialized state -- and then stimulate their development into cells with pancreatic properties.
Promising success in animal experiments
A gene called TGIF2 plays a crucial role in the process. TGIF2 is active in the tissue of the pancreas but not in the liver. For the current study Dr. Nuria Cerda Esteban, at the time a PhD student in Dr. Spagnoli's lab, tested how cells from mouse liver behave when they are given additional copies of the TGIF2 gene.
In the experiment, cells first lost their hepatic (liver) properties, then acquired properties of the pancreas. The researchers transplanted the modified cells into diabetic mice. Soon after this intervention, the animals' blood glucose levels improved, indicating that the cells indeed were replacing the functions of the lost islet cells. The results bring cell therapies for human diabetic patients one step closer to reality.
The obvious next step is to translate the findings from the mouse to humans. The Spagnoli lab is currently testing the strategy on human liver cells in a project funded in 2015 by the European Research Council. "There are differences between mice and humans, which we still have to overcome," Spagnoli says. "But we are well on the path to developing a 'proof of concept' for future therapies."
Nuria Cerdá-Esteban et al. (2017): "Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2." Nature Communications. doi:10.1038/ncomms14127
Vera Glaßer | EurekAlert!
Switch-in-a-cell electrifies life
18.12.2018 | Rice University
Plant biologists identify mechanism behind transition from insect to wind pollination
18.12.2018 | University of Toronto
Researchers from the University of Basel have reported a new method that allows the physical state of just a few atoms or molecules within a network to be controlled. It is based on the spontaneous self-organization of molecules into extensive networks with pores about one nanometer in size. In the journal ‘small’, the physicists reported on their investigations, which could be of particular importance for the development of new storage devices.
Around the world, researchers are attempting to shrink data storage devices to achieve as large a storage capacity in as small a space as possible. In almost...
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
18.12.2018 | Materials Sciences
18.12.2018 | Physics and Astronomy
18.12.2018 | Physics and Astronomy