The ability to maintain haematopoietic stem cell (HSC) populations in vitro would provide large societal benefit. Haematopoietic cancers, such as leukaemia, arise for genetic alterations in HSCs. The current approach is to kill malignant HSCs and then use bone marrow transplantation to provide long-term reconstituting (LTR) HSC populations to regenerate the blood system. Bone marrow transplantation is, however, a one donor – one patient therapy and donors are in urgent demand. There have been many attempts to maintain LTR-HSCs in vitro, out of the bone marrow niche. However, out of their niche HSCs either die or expand rapidly losing long-term reconstituting phenotype as they grow; these LTR HSCs are critical to provide to patients as they are the cells required to engraft and to repopulate the marrow to produce new blood cells.
Working with Manchester BIogel’s synthetic Peptigel® hydrogels, this project will focus on bioengineering in vitro HSC niches. Using physical cues such as stiffness and solid-phase growth factor presentation, and biological cues such as other cells, we will develop microenvironments where LTR-HSC populations can be maintained in the laboratory. Being able to conserve LTR-HSC number in vitro is important as it allows us to study and manipulate the cells. For example, in this new project, we will develop CRISPR approaches to edit the stem cells. This is important as e.g. chronic myloid leukaemia is typified by the BCR-ABL mutation. If we can edit out and correct such mutations, then we can envisage ways to repair patients’ cells ex vivo and then provide them back to the patients - removing the cancer and regenerating a disease free blood system with their own cells.
This project is based in the Centre for the Cellular Microenvironment (https://glasgow.thecemi.org ) a well-funded, dynamic research environment and would give the student insight into both academic and industrial research settings. It would suit a student with a strong background in bioengineering / cell biology, biotechnology or related background. Informal enquiries to [email protected].
Closing date: 29th Feb 2020 – looking to start around April 2020.