Age-related changes in adult stem cells.
PhD Supervisor(s): Dr Alexandra Stolzing
One of the aims in regenerative medicine is the use of allogeneic cell products and the necessary up-scaling required to be economic. However one drawback of this approach is that cells age during expansion and that we have currently no good marker to indentify the limit of expansion and the recognition of therapeutic inactive cells.
Several recent studies have shown that highly expanded MSC are therapeutic not as active as low level passaged cells.
Some very un-reliable intracellular aging marker exists for mesenchymal stem cells, but for these markers the cells need to be destroyed and the amount of cells needed is large.
The goal of the project is to find a reliable aging marker for human mesenchymal stem cells from different tissue sources (placenta derived, bone marrow derived, teeth pulp derived).
The marker should best be secreted by the cells for easy continuous in process control, however we will also include some intracellular markers based on the epigenome of the cells.
This will allow us to predict the therapy outcome for expanded MSC minimising failure.
From former studies of our group we have some good candidates based on an epigenetic study (1).
Aims:
1) Validating epigenetic biomarkers of aging
2) Applying novel non-invasive measurements including analysing secreted factors
3) Analysing the headspace of the cell cultures for aging signs
Novel Engineering: This project will explore the use of volatile chemicals in the gasphase of cell cultures to indentify the expansion limit. For this we will design a new sampling device of the gasphase and integrate it into bioreactor and automated cell expansion system.
