SSA - Defining the stromal cell subtypes controlling bone homeostasis and haematopoiesis.

Lead Research Organisation: University of York
Department Name: Biology

Abstract

Adult mesenchymal stem cells (MSCs) are located in bone marrow and are able to differentiate into bone, cartilage and fat to support the maintenance and repair of the skeleton. There is ample evidence that MSCs are also able to control other aspects of marrow function, but progress has been hampered as MSCs are difficult to distinguish from other stromal cell types because they lack specific identifying markers. We have generated a panel of immortalised, single cell-derived MSC lines to enable in-depth analysis of MSC subtype function with specific, distinguishing characteristics. These MSC lines display widely variable differentiation competencies but we have not explored other MSC functions including how they support haematopoietic cell behaviour and the production of different blood cell types, as well as immunoregulatory behaviour. This project will make use of this unique MSC resource to determine how MSC subtypes contribute to the support of haematopoietic stem cells and their differentiation into specific cell types. We will use screening techniques to identify novel MSC markers combined with in vivo studies to determine niche compositions and location. Collectively, this work will unveil previously unrecognised cell-cell interactions that determine stem cell behaviour across different lineages.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
1792529 Studentship BB/M011151/1 30/09/2016 30/03/2021 Andrew Stone
 
Description In bone marrow there are a mixture of cells that contribute to repair and maintenance of the skeleton. These cells are known as mesenchymal stromal cells or MSCs. MSCs can perform variable functions and we are trying to tell apart mixed populations of these cells. We are able to see that different MSCs release different molecules and proteins into their environment. These proteins could help to explain how these cells perform different functions. We have also been able to show that one of the MSCs is capable of changing the shape and movement behaviour of another MSC due to the molecules it releases.
Exploitation Route This can be developed upon for the production of cell based therapies.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Facilities Award from Department of Biology
Amount £4,560 (GBP)
Organisation University of York 
Sector Academic/University
Country United Kingdom
Start 07/2017 
End 01/2018
 
Description Honor Fell Travel Award
Amount £180 (GBP)
Organisation Company of Biologists 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2019 
End 09/2019
 
Description ColVI knockout mice study 
Organisation University of Padova
Country Italy 
Sector Academic/University 
PI Contribution We are providing expertise in the area of bone marrow microenvironment and MSC biology. We will be receiving samples of bone tissue from ColVI knockout mice generated in Italy. We will then apply immunofluorescence techniques to characterise the bone marrow for stromal cells and vascular architecture.
Collaborator Contribution Our partners in Italy are providing the mouse tissues and will help to interpret any findings from the femur samples.
Impact No outputs yet - it is a new collaboration
Start Year 2019
 
Description NanoString platform for quantifying miRNA content of Extracellular Vesicles derived from stromal cell subsets 
Organisation Newcastle University
Department Newcastle University Medical School
Country United Kingdom 
Sector Academic/University 
PI Contribution Produced extracellular vesicles from stromal subsets for characterisation in Newcastle.
Collaborator Contribution Provided a centre where I could isolate RNA from MSC derived extracellular vesicles (EVs) before quantifying the RNA. Provided codesets for NanoString and access to the technology which allowed me to then quantify individual miRNAs found in MSC EVs.
Impact Joint abstract submitted to European Calcified Tissue Society meeting in May 2019.
Start Year 2018
 
Description Concurrent oral presentation at the Bone Research Society/Bone and Orthopaedic research society joint meeting in Cardiff in September 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I presented my work to the audience at the BRS/BORS conference in the form of a concurrent oral presentation and answered questions afterwards. This provided an excellent opportunity to disseminate our findings and discuss with colleagues in the field.
Year(s) Of Engagement Activity 2019
URL https://boneresearchsociety.org/media/documents/BRS_BORS_Final_programme_ws.pdf
 
Description Patient and Public Engagement with Genever Lab at University of York 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Held an open interaction day where we presented some of our work on MSCs and their roles in arthritis and how we are trying to improve outlooks for patients with arthritis through both better understanding of the disease and improvements to available treatments. Around 20-30 members of the public attended the event, the majority of whom have some form of arthritis. We had a good dialogue with patients in order to understand what they want from our research in order to improve their lives, this will help to guide our research in the future.
Year(s) Of Engagement Activity 2018
URL https://www.geneverlab.info/single-post/2018/08/29/First-Patient-Involvement-Day
 
Description Poster and Poster Presentation at ECTS 2019 in Budapest 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I presented a poster and short oral presentation at the European Calcified Tissue society conference in Budapest in May 2019 on the project work I have performed to date. This allowed discussion with colleagues in the bone marrow field and good networking opportunities. It also made colleagues from our area aware of the work we were undertaking.
Year(s) Of Engagement Activity 2019
 
Description Presentation at the BBSRC White Rose DTP mechanistic biology symposium in December 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact This is a yearly internal conference where final year PhD students submit abstracts for presentations. I was selected to give an oral presentation which allowed me to discuss and disseminate my findings from my research with fellow postgraduates from across the white rose DTP.
Year(s) Of Engagement Activity 2019
 
Description Presentation of research at the Tissue Engineering Society meeting 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Gave a short talk on research from the Genever Lab that had been performed previously which was being continued as part of my PhD project. The Tissue and Cell engineering society meeting was attended by around 200 research scientists in the field of cell and tissue engineering. Dissemination of research and discussion of research.
Year(s) Of Engagement Activity 2017
 
Description YorNight stand 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Our research group ran a stand to engage with the general public and disseminate information about arthritis and research into stem cells.
Year(s) Of Engagement Activity 2018
URL https://www.geneverlab.info/single-post/2018/12/13/December-round-up