Regulation of mesenchymal stem cells during vascular remodelling by platelet-derived growth factor receptor-alpha.

Lead Research Organisation: University of Manchester
Department Name: Life Sciences

Abstract

Our research will be presented orally at scientific meetings and conferences, and in peer-reviewed research papers, review-type articles. We will publish articles in magazines and newsletters aimed at biotechnology and healthcare industries.
A likely avenue for lay reporting will be communicating with school students as part of our outreach programmes in which students visit the host laboratory, or through the Manchester Museum, which organises regular science days. Our laboratory regularly hosts work experience students.

Technical Summary

Mesenchymal stem cells in bone marrow and perivascular niches act as a source of multipotential cells for tissue regeneration. We have discovered that, in bone marrow-derived MSC, vascular endothelial growth factor-A activates platelet-derived growth factor receptors which, in turn, regulate migration, proliferation and vascular differentiation. We also have evidence for the involvement of neuropilin-1, beta1 integrins and vascular extracellular matrix in platelet-derived growth factor receptor activation. Building on these advances, this proposal is to study ligand-specific platelet-derived growth factor receptor-alpha signalling in mesenchymal stem cells, and its role in vascular remodelling.
 
Description BBSRC CASE Studentship
Amount £50,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2008 
End 09/2011
 
Description BBSRC CASE Studentship
Amount £50,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2007 
End 09/2010
 
Description EPSRC Novel Technologies for Stem Cell Science (co-I)
Amount £2,575,000 (GBP)
Funding ID EP/H046070/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start  
 
Description MRC Inducible Pluripotent Stem Cell Supplement
Amount £50,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 06/2009 
End 02/2011
 
Description MRC-BHF Strategic Award
Amount £780,000 (GBP)
Funding ID G0902170 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2011 
End 12/2013
 
Description Manchester Biomedical Research Centre BRC) Small Grant Scheme
Amount £20,000 (GBP)
Organisation National Institute for Health Research 
Department NIHR Manchester Musculoskeletal Biomedical Research Unit
Sector Academic/University
Country United Kingdom
Start 01/2009 
End 06/2009
 
Description Wellcome Trust PhD studentship
Amount £150,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2007 
End 09/2010
 
Title PDGF receptor expression vectors 
Description Human PDGF receptors alpha and beta knockdown and knock-in vectors (retroviral), mutants, with and without tyrosine signalling mutations. Also, human neuropilin-1 full-length and ectodomain costructs. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact New insights into how the PDGF receptor signalling pathways regulate mesenchymal stem cells. 
 
Description Investigation of PDGF receptor interactions with neuropilin-1. 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution I am PhD supervisor and I wrote the PhD proposal.
Collaborator Contribution CASE PhD studentship (AZ provided reagents to assist in analysing PDGF receptor interactions with neuropilin-1).
Impact I was an invited speaker at the Biochemical Society international meeting on Angiogenesis at the University of Chester meeting, in July 2009. My PhD student presented a poster.
Start Year 2008
 
Title Vascular tissue engineering 
Description Preliminary development of small-diameter tissue engineered vascular grafts, incorporating elastic fibre reagents and adult progenitor cells. 
Type Therapeutic Intervention - Cellular and gene therapies
Current Stage Of Development Initial development
Year Development Stage Completed 2009
Development Status On hold
Impact No translational achievements to date. Small grant funding from Manchester Biomedical Research Centre for small diameter graft design (£20K). The application of extracellular matrix coatings of graft scaffolds - one year contract with Johnson&Johnson (ATRMUS); now closed. 
 
Description Seminars at UK Institutions 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Kings College London (Denmark Hill Campus; vascular tissue engineering)
Manchester (Biochem Soc meeting; elastic fibres)
Bristol University (elastic fibres)
Edinburgh University (progenitor cells)
Keele University (vascular tissue engineering)
Newcastle University (progenitor cells)
Birmingham University (progenitor cells)

Collaborative links.
Year(s) Of Engagement Activity 2008,2009,2010,2011
 
Description UK National Stem Cell Network (UKNSCN) meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Paper Presentation
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact April 2008. Edinburgh. Invited speaker. April 2009. Workshop leader (Mesenchymal Stem Cells)

New collaborative links.
Year(s) Of Engagement Activity 2008,2009