Involvement of mesenchyma in healthy and malignant bone marrow
Research type
Research Study
Full title
Pilot study to investigate the interaction between bone marrow mesenchymal stromal cells (MSC) and haematopoietic stem cells (HSC) in health and malignant disease both pre- and post-chemotherapy treatment within an adult haematology outpatient clinic setting.
IRAS ID
233487
Contact name
Jen May
Contact email
Sponsor organisation
University of the West of England
Duration of Study in the UK
4 years, 0 months, 1 days
Research summary
This pilot study will contribute towards a PhD project funded by the University of the West of England (UWE) aiming to investigate the interactions between two key populations of cells in the bone marrow (BM). Whilst haematopoietic cells (HSC) produce mature blood cells, mesenchymal stromal cells (MSC) are critical in supporting this process. In health, there is significant cross-talk and interaction between HSC and MSC.
Previous work shows that in haematological malignancies, however, these interactions can result in resistance to chemotherapy and consequently a poor outcome for the patient. The mechanisms by which this occurs require further study.
This study will optimise a cell line model previously developed at UWE to incorporate HSC and MSC from individuals with a haematological malignancy, as well as those with healthy BM. Resistance of leukaemic cells with and without MSc will be studied using cytotoxicity and genotoxicity assays, together with a bioluminescent bacterial biosensor developed at UWE to detect chemosensitivity. Additionally, a variety of assays including proteomic and metabolic studies will be used to investigate potential mechanisms by which this may occur.
Individuals attending the haematology outpatient clinic at the Royal United Hospital, Bath, will be recruited into one of five groups (acute myeloid leukaemia at diagnosis, acute myeloid leukaemia post chemotherapy, other haematological malignancy at diagnosis, other haematological malignancy post chemotherapy, healthy BM) based on diagnosis and treatment history, aiming to obtain 10 datasets per group. Individuals approached will be undergoing a BM aspirate as part of standard care, and if willing to participate, excess BM will be collected for this study to enable isolation of both HSC and MSC.
Elucidation of the mechanisms involved in this chemo-resistance phenomenon may in future allow identification of patients where this may be an issue clinically and therefore potentially enable more effective therapy to be delivered.REC name
HSC REC A
REC reference
18/NI/0036
Date of REC Opinion
13 Feb 2018
REC opinion
Favourable Opinion