UKRMP Hub: The Engineered Cell Environment.

Lead Research Organisation: University of Edinburgh
Department Name: MRC Centre for Regenerative Medicine

Abstract

Stem cells have great potential in medicine as they can grow into many different cell types in the body. Our aim is to create a research network of scientists and clinicians working towards understanding how stem cells behave within their normal tissue environment. The environment or "Niche" within the body that surrounds stem cells has a profound effect on the behaviour of stem cells and whether they can repair damaged organs. By understanding how the Niche influences stem cells in tissues we aim to use this knowledge to develop future treatments for serious untreatable diseases.

To promote "healthy regeneration" in tissues and organs, we will use 2 main strategies: (1) test drugs and small synthetic molecules in experimental models of organ injury. We hope to influence the behaviour of the stem cells within their Niche environment by adding drugs. (2) Another way of treating damaged tissue and organs is to transplant stem cells or cells from stem cells into the damaged organ - this kind of treatment is known as a cell therapy and an example of this used today to treat patients is bone marrow transplantation. Whilst this treatment is successful for many diseases, in some cases this treatment does not work and the cells do not grow well. Our network wants to understand why the Niche environment does not always allow cells to grow well. We hope to develop novel treatments using cell transplantation to promote healthy regeneration of tissue and organs.

We aim to develop treatments for patients who are currently suffering from untreatable diseases affecting the (a) liver, (b) joints and the (c) lungs.

(a) Liver disease is the 5th most common cause of death in the UK. The current treatment for patients with end-stage cirrhosis and acute liver failure is a liver transplant, however organ availability cannot meet demand and many patients die waiting for an organ. Those who do undergo transplantation require lifelong immunosuppression with concomitant risks of infection, cancer, renal and cardiovascular disease. Thus, there is a clear imperative to identify alternatives treatments. One of our research themes will investigate healthy regeneration of the liver using drugs or cell therapies.

(b) Another research theme from our Hub investigates new treatments for Osteoarthritis (OA) which is one of the fastest most rapidly increasing major health conditions, with over 8 million people affected in the UK alone. Whilst end-stage disease is suited to joint replacement, there is an urgent need to address earlier disease stages with repair and regenerative strategies.

(c) We are also investigating regeneration of the lung; chronic lung disease is responsible for 6 million inpatient bed days a year in the UK. There is a clear unmet need for this research to be carried out.

We will bring together scientists with the different kinds of expertise that we think are required to tackle these scientific and medical challenges. By linking these experts with doctors working in these clinical areas and helping them to collaborate together we hope to make more rapid progress in the development of new treatments for these chronic diseases.

Technical Summary

The UKRMP Engineered Cell Environment Hub (ECEH) aims create a platform, linking excellence in the regenerative biology of the stem cell niche with experimental medicine to translate regenerative therapies to the clinic. We will bring together leading scientists in regenerative biology, stem cells, niche biology, phenotypic screening, safety and transplant immunity with clinician scientists working in regenerative medicine in a highly collaborative network.

We will develop two linked translational regenerative strategies:
(1) Developing Cell Therapies for Damaged Organs: We will use our knowledge of niche biology to optimise cells for therapy. Artificial niches will be constructed that mimic healthy tissue and facilitate effective cell therapy. Pluripotent and adult human stem cell sources will be optimised in vitro and tested in our pre-clinical models of liver, joint and lung repair. Immune responses to the transplanted cells will be assayed in relevant humanized mouse models.
(2) Promoting endogenous repair of damaged organs:Using stem cells in vitro, we will create high content 2D and 3D phenotypic screens for liver, cartilage and lung repair. We will study the behaviour of stem cells in their niche aiming towards optimising endogenous repair and use FDA approved compound libraries to identify potential drugs and biological agents for translation.

The Hub is structured with 3 basic underpinning scientific areas and technologies: (a) Understanding and improving the physical properties of Aged and Injured Tissue Niches; (b) Developing Artificial Wnt Niches to act as regenerative signals for tissue formation and repair; (C) High content phenotypic screening for the discovery of novel targets for endogenous repair.

We have 3 clinical translational exemplars: liver (WP1), joint (WP2), lung (WP3) repair. Each theme is led by a pair of investigators with complimentary expertise, common underpinning biology and enabling technologies that span the WPs.

Planned Impact

The disease exemplars that will be investigated during the course of this project are liver regeneration, lung regeneration and joint regeneration.

Liver disease is the 5th commonest cause of death in the UK and the deaths from cirrhosis are rapidly rising (British Liver Trust, www.britishlivertrust.org.uk). 16,087 people in the UK died from liver disease in 2008, a 4.5% increase since 2007. Most liver deaths were in people under 70, while one in 10 deaths of all people in their 40s were from liver conditions. The only curative option for end-stage liver disease is liver transplantation but donor organ availability cannot meet current demand and many patients die whilst waiting for a suitable organ; may patients with severe liver disease are not eligible for transplantation.

Chronic lung disease is responsible for 6 million inpatient bed days a year in the UK. Chronic Obstructive Pulmonary Disease (including emphysema) and idiopathic pulmonary fibrosis are both now thought to be diseases of epithelial damage and failed repair, with no treatments that reverse lung function decline.

Osteoarthritis (OA) is a rapidly increasing health burden, affecting over 8 million people in the UK. Whilst end-stage disease is suited to joint replacement, repair and regenerative strategies could address earlier disease stages.

It is foreseen that the results generated from the proposed cell therapy research would allow further funding to be leveraged (this would be the subject of a future funding application) in order to head towards a Phase 1 study. It is likely that this next stage of the research would involve input from the Cell and Gene Therapy Catapult.

If any pertinent results are generated from the endogenous repair screening work packages, the investigators would look to partner with an appropriate Pharma/biotech partner in order to advance towards making a clinical impact. It is proposed to screen FDA approved libraries in the first instance which would mean that there is the potential to move towards clinical studies in an efficient manner.

The MRC Centre for Regenerative Medicine has a strong outreach program which will help to disseminate results to appropriate patient groups and stakeholders. To maximise the scientific and clinical impact from the regenerative medicine the investigators will closely involve the UKRMP network. The investigators involved have a record of publishing in high impact journals with wide readership in the relevant scientific and clinical communities. Any intellectual property generated during the course of the project will be appropriately protected by the relevant partner University/Universities and exploited by the relevant technology transfer organisation.

Publications

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Armstrong JPK (2020) A blueprint for translational regenerative medicine. in Science translational medicine

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Campana L (2021) Liver regeneration and inflammation: from fundamental science to clinical applications. in Nature reviews. Molecular cell biology

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De La Fuente AG (2020) Changes in the Oligodendrocyte Progenitor Cell Proteome with Ageing. in Molecular & cellular proteomics : MCP

 
Description Immunogenicity test platform - in vitro and in vivo
Amount £925,636 (GBP)
Funding ID MR/S020934/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2019 
End 02/2022
 
Description Macrophage Therapy for Acute Liver Failure
Amount £2,665,628 (GBP)
Funding ID MR/T044802/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 12/2020 
End 11/2025
 
Description Manipulating the peripheral nerves of the niche to improve epithelial regeneration of the salivary gland
Amount £609,772 (GBP)
Funding ID MR/S005544/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2018 
End 04/2021
 
Description Mobilising epithelial stem cells for human lung regeneration
Amount £609,773 (GBP)
Funding ID MR/S005579/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2018 
End 04/2021
 
Description Towards human lung regeneration: study of cell interactions and epithelial maturation in human lung development
Amount £60,000 (GBP)
Funding ID M899 
Organisation Rosetrees Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2019 
End 09/2021
 
Description UKRMP Strategic Funding Call
Amount £749,764 (GBP)
Funding ID MR/T015489/1 
Organisation UK Regenerative Medicine Platform 
Sector Academic/University
Country United Kingdom
Start 12/2019 
End 11/2022
 
Description UKRMP Strategic Funding Call
Amount £749,818 (GBP)
Funding ID MR/T015594/1 
Organisation UK Regenerative Medicine Platform 
Sector Academic/University
Country United Kingdom
Start 11/2019 
End 10/2022
 
Description UKRMP/Immunology: Defining the role of tissue-resident immune cells in alveolar epithelial cell regeneration
Amount £886,110 (GBP)
Funding ID MR/S020918/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2019 
End 02/2022
 
Description Universal cells to overcome HLA barriers in regenerative medicine
Amount £836,002 (GBP)
Funding ID MR/S02090X/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 12/2018 
End 11/2021
 
Description Article in Financial Times about 3D printing of tissue 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Article in FT about 3D printing of tissue
Year(s) Of Engagement Activity 2019
 
Description Article in local news covering UKRMP fellow Elaine Emmerson's research 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Media (as a channel to the public)
Results and Impact Interviews with De Elaine Emmerson and artist in residence Emily Fong about a sci-art project focusing on Elaines work on repairing salivary gland function following radiotherapy for throat cancer.
Year(s) Of Engagement Activity 2019
URL https://www.thecourier.co.uk/fp/news/local/fife/995272/fife-artist-spends-months-in-science-lab-for-...
 
Description Castlebrae Community High School Workshops and visits 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Working in partnership with the local schools cluster we organise a programme of workshops with pupils, talks and visits to our facility.
Year(s) Of Engagement Activity 2018,2019
 
Description Community Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Now in its third year, the Craigmillar Community Science Festival is held on the last Friday in March in the run up to the Edinburgh International Science Festival. Held in partnership with The Community Alliance Trust at The White House Kitchen Community Cafe, the festival sees young people in the community demonstrating science to Festival-goers alongside scientists from the Centre and elsewhere at The University of Edinburgh.
Year(s) Of Engagement Activity 2018,2019,2020
 
Description G-Lands Workshops for patients 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact A series of workshops led by Dr Elaine Emmerson (UKRMP Fellow) with 6 people with experience of throat cancer based on artwork drawing from Dr Emmerson's work G-Lands by artist Emily Fong.
Year(s) Of Engagement Activity 2022
URL https://www.ed.ac.uk/regenerative-medicine/public-engagement/g-lands
 
Description G-Lands story in University Impact Webpage 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Article about G-Lands Art-Science project on Edinburgh Impact website
Year(s) Of Engagement Activity 2021
URL https://www.ed.ac.uk/impact/research/future-health-and-care/the-art-of-science
 
Description Guest on BBC Naked Scientists Radio Show 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Interview on radio show
Year(s) Of Engagement Activity 2019
 
Description Guided virtual laboratory tour 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact As a satelite event of the Swallow's Head and Neck Cancer Support Charity International Head and Neck Cancer Conference 2020, Dr Elaine Emmerson led an online virtual tour of her laboratory using the Centre online virtual tour, videos and interviews with her research team.
Year(s) Of Engagement Activity 2020
URL https://www.ed.ac.uk/regenerative-medicine/about/tour
 
Description MRC Centre for Regenerative Medicine virtual online tour 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A new online virtual tour of the Centre, incorporating audio of a PhD student tour "guide" . Over 20 locations around the Centre. Used to support visits, schools workshops, 3rd sector visits etc. >10,000 impressions on Twitter, >500 unique page views. Images also available on our google.com profile.
Year(s) Of Engagement Activity 2019
URL http://www.crm.ed.ac.uk/tour
 
Description MRC Festival of Medical Sciences 25th June 2018 - CRMat10 Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Supporters
Results and Impact A reception to celebrate 10 years of the Centre. Presenters included directors, staff, students and community partners. It was attended by a long standing donor of the Centre, one of the first PhD students and our local community school partners. Awards recognised significant contributions to the MRC CRM over the past 10 years and included past and present members of the professional services team. Staff commented that they found the event inspiring and appreciated its inclusiveness. The event generated a lot of interest on social media
160 Engagements for one Twitter post https://twitter.com/crm_edinburgh/status/1010208591712870401
204 Engagements for one Facebook post https://www.facebook.com/CentreForRegenerativeMedicine/posts/1691853487599976
This is well above average for our social media channel and among the top 3 posts in the year.
Year(s) Of Engagement Activity 2018
URL http://www.crm.ed.ac.uk/CRMat10awards
 
Description MRC Research Showcase at the Scottish Parliament 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact MRC Research Showcase at the Scottish Parliament highlighting biomedical research within Scottish Universities funded by the MRC.Professor Hay reported that he will have followup discussions with Miles Briggs MSP about health policy.
Year(s) Of Engagement Activity 2018
URL https://twitter.com/crm_edinburgh/status/1093224653341057025
 
Description News article in Edinburgh Evening News talking about the work of UKRMP Fellow Elaine Emmerson 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Media (as a channel to the public)
Results and Impact News story in Edinburgh Evening News about Elaine Emmerson's (UKRMP Fellow) research into salivary gland function following radiotherapy.
Year(s) Of Engagement Activity 2019
URL https://www.edinburghnews.scotsman.com/health/top-medical-researcher-lead-throat-cancer-treatment-pl...
 
Description Online article on The Naked Scientist 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Professor Hay wrote an article for The Naked Scientist called "The future for artificial livers"
Year(s) Of Engagement Activity 2020
URL https://www.thenakedscientists.com/articles/science-news/future-artificial-livers
 
Description Press release: Stem cell liver implants show promise 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Press release from CRM resulting in media coverage on websites and in newspapers.
Scottish Daily Mail
https://www.pressreader.com/uk/scottish-daily-mail/20180828/281977493484972
Online
https://www.fiercebiotech.com/research/growing-human-stem-cells-into-functional-3d-liver-tissue
https://www.rdmag.com/article/2018/08/new-liver-tissue-implants-showing-promise
MRC website
https://mrc.ukri.org/news/browse/liver-tissue-implants-show-promising-support-of-liver-function/
Year(s) Of Engagement Activity 2018
URL http://www.crm.ed.ac.uk/news/stem-cell-liver-implants-show-promise
 
Description RSE Lecture: Innovation in Organ Transplantation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Lecture given at Royal Society of Edinburgh: Innovation in Organ Transplantation
Year(s) Of Engagement Activity 2018
 
Description Radio scotland interview and press coverageon Macrophage Cell Therapy 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact Professor Stuart Forbes was interviewed on BBC Radio Scoland prime time show Good Morning Scotland about the potential of Macrophage Cell Therapy as a result of a press relaease about new University of Edinburgh spinout company Resolution Therapeutics Ltd. This story was also covered in The Herald (see link).
Year(s) Of Engagement Activity 2020
URL https://www.heraldscotland.com/business_hq/18915162.edinburgh-university-spin-out-secures-26-6m-trea...
 
Description Regeneration Innovation 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Workshop to encourage and stimulate translation and commercialisation of research from the CRM. Speed networking and an innovation competition were included as acitvities as well as presentations from existing industry collaborations.
Year(s) Of Engagement Activity 2018
 
Description Research Insights Online Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Dear Elaine Emmerson presented a live online talk: "Rebuild and repair: Seeking saliva after throat cancer" as part of the University of Edinburgh College of Medicine and Vet Medicine series Research Insights. Over 100 people logged in to this online presentation and engaged in questions.
Year(s) Of Engagement Activity 2021
URL https://www.ed.ac.uk/medicine-vet-medicine/news-events/college-events/research-insights/rebuild-and-...
 
Description Sci-art workshop and laboratory tour as part of the Luminate Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact A 2 hour workshop based in the Centre for Regenerative Medicine and run by artist in residence Emily Fong.
Year(s) Of Engagement Activity 2019
URL https://twitter.com/emilyfongstudio/status/1131104651728830465?s=20
 
Description SciArt Workshops 
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 SciArt Workshops run with CSCRM, KCL including the Great Exhibition Road Festival Workshops
Year(s) Of Engagement Activity 2019
 
Description Science Festival discussion about use of animals in research 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact UKRMP Fellow Elaine Emmerson contributed to this MRC funded event "Animals in Research - what are the alternatives? The event was shortlisted and won a public engagement award at the Understanding Animal Research awards in Nov 2019 https://www.ed.ac.uk/research/animal-research/news/open-approach-to-animal-research-earns-accolade
Year(s) Of Engagement Activity 2019
URL https://twitter.com/crm_edinburgh/status/1114548415378206720?s=20
 
Description The Naked Scientist 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Professor Hay was interviewed as part of a Naked Scientist broadcast "Artificial liver progress"
Year(s) Of Engagement Activity 2020
URL https://www.thenakedscientists.com/podcasts/short/artificial-liver-progress
 
Description £4M bid to find therapies that prompt tissues to repair 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Press release to highlight successful award of funding for UKRMP2 Hub.
Tom Feilden from the Today Programme was interested in doing a follow up to this. This was subsequently delayed. We intend to follow up.
University press release https://www.ed.ac.uk/news/2018/ps4m-bid-to-find-therapies-that-prompt-tissues-to
Year(s) Of Engagement Activity 2018
URL http://www.crm.ed.ac.uk/news/4m-bid-find-therapies-prompt-tissues-repair