Fundamental mechanism of aging could improve IVF success
A reNEW Copenhagen team, led by Professor Joshua Brickman, demonstrate that by changing their diets, stem cells can rejuvenate and turn into ‘super stem cells’, which are more effective at making other cells, and perform exceedingly well when transplanted into a mouse embryo. This insight, published in EMBO Journal, could have many potential applications, including to improve the success of IVF treatment.
In this study, researchers have developed a new culture medium (EMM) for culturing embryonic stem cells (ESCs), which increases their potential to differentiate into other cells and to perform highly effectively well when transplanted into embryos.
“In the same way that caloric restriction has been shown to have many long-term health benefits in humans, our research shows that the same principle applies to stem cells as well. This has implications for improving many stem cell-based therapies,” said Professor Joshua Brickman.
By switching glucose in the media to galactose, the cell's primary source of energy generation is blocked, and the ESCs are restricted to a metabolic process known as oxidative phosphorylation, which metabolizes other nutrients in the cell, primarily lipids. This change in their nutrient source reprograms ESCs to an earlier stage of development, enhancing their ability to differentiate. By rejuvenating embryonic stem cells and improving their function in this way, this research could lead to further refine stem cell-based therapies.
“Our research illustrates that eliminating glucose metabolism in stem cells makes them into “super stem cells”, which has a wide variety of implications for improving stem cell-based therapies to treat many diseases that are prevalent today,” said Associate Investigator Robert Bone.
The team is now seeking to investigate how this change in the type of sugars fed to stem cells could work on a variety of cell types and aging models. For example, could this media revitalize liver cells? Is it a way to increase function in different stem cell populations for regenerative medicine?
“Our paper uncovers a fundamental mechanism of aging. We find that cells become less fit as they receive less precise instructions. Imagine listening to someone in a crowded restaurant, where what they hear is both determined by the volume of the person they are speaking to and the ambient level of noise. As cells get older, they hear their genetic instructions less well because the instructions are both reduced in volume, and confounded by greater levels of background noise,” said Professor Joshua Brickman.
While the possibilities for improving disease treatments with this work are broad, the team are particularly interested in the implications for improving IVF outcomes. It is known from a previous study that the presence of future yolk sac signatures in human embryos is the single best predictor of successful pregnancy in IVF.
“EMM culture enables ESCs to generate these cells, and so culturing embryos in similar conditions could result in a higher rate of successful pregnancies,” said Associate Investigator Robert Bone.
Read the paper.