Bile acid supports the production of blood stem cells

Researchers have not yet managed to get the blood-forming stem cells to produce new stem and blood cells in a laboratory. The problem with making blood stem cells proliferate outside the body is that the artificial growth gives rise to an accumulation of abnormal proteins in a part of the cell called the endoplasmic reticulum, ER. Among other things, this so-called ER stress, if the stress is severe and chronic, cause cell death.

Kenichi Miharada, researcher at the Department of Laboratory Medicine, has previously shown that it is possible to reduce ER stress chemically by adding bile acids to the cell culture. Bile acids, which are produced naturally in the liver and stored in the gallbladder, support the protein production during the cell division process.

"Compared to other ways of trying to develop stem cells to treat blood diseases, this method is safer and quicker, because it does not involve using any artificial substances or any genetic modifications, merely a substance that already exists inside the body," explains Kenichi Miharada.

Bile acids are normally found in adults, to help digest food. However, in studies of pregnant mice, Kenichi Miharada found large amounts of bile acids also inside the fetus.

"fetuses produce small amounts of bile acids on their own, but here we are talking about much larger quantities. The bile acid appears to be produced by the mother and then transferred to the fetus via the placenta," says Kenichi Miharada.

A large part of bile acid is in fact toxic for cells, but undergoes a purification process when transferred through the placenta, letting only harmless bile acid through to the fetus. It has been known that bile acid is produced in the fetal liver, but not why. Kenichi Miharada discovered that bile acid supports the production of blood stem cells in the fetal liver, and enables them to develop normally. The additional contribution from the mother is important for the fetus to develop normally.

"Our hypothesis is that the consequence of a damaged placenta, which for various reasons is unable to transfer bile acids to the fetus, can lead to leukemia or other blood diseases later in life, and we will continue our research to see if this hypothesis holds up," concludes Kenichi Miharada.