RegenVOX. Stem-cell based, tissue engineered laryngeal replacement.

Lead Research Organisation: University College London
Department Name: Ear Institute

Abstract

Irreversible damage to the larynx (?voice-box?) can result in considerable reduction in quality of life with problems breathing, speaking and swallowing, thus preventing the normal integration of people into society. The creation of a complete replacement would require complex muscular activity which is beyond the scope of the work we propose here. However, the successful restoration of critical structural support and a new lining would restore the joys of speech, swallowing and, indeed, normal human interaction to many people. We will build on the breakthrough we achieved by regenerating the trachea (?windpipe?) of a young woman in Spain by using patients? own stem cells and mucous membrane cells, combined with a non-rejecting matrix support, to restore parts of the larynx destroyed by disease, accident or cancer. This would be a major breakthrough for surgery and the lessons learnt will help the development of regenerative cures for a host of other diseases.

Technical Summary

The overarching aim of this project is to optimise laryngeal cell and scaffold production prior to performing preclinical studies necessary for clinical trials, and demonstrate the feasibility of stem-cell based partial laryngeal regeneration in a pig model. Specific aim 1 is to develop Standard Operating Procedures to include Release Criteria and In-Process Quality Control for production of mesenchymal stem cell derived chondrocytes, airway epithelium and laryngeal scaffolds (synthetic and biologic). Specific aim 2 is to perform feasibility studies of partial laryngeal regeneration using human stem cells in pigs. Specific aim 3 is to maximise the economic and health benefits arising from the RegenVOX programme. This project forms part of an integrated programme of tissue regeneration at UCL. The long-term aim of this NHS- and UCL-backed programme is to deliver a new generation of hollow-organ therapies into clinical practice. We believe we possess a critical mass of multidisciplinary personnel and facilities (significantly reducing costs requested), the relevant commercialisation experience, and a high probability of outcome delivery within 2 years. We are unique in our ability to ability to deliver a first in man implants (as seen with our tracheal implant programme).

Publications


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Ansari T (2016) Stem Cell-Based Tissue-Engineered Laryngeal Replacement. in Stem cells translational medicine


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Arulanandam S (2017) Laryngological presentations of Ehlers-Danlos syndrome: case series of nine patients from two London tertiary referral centres. in Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery


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Birchall M (2016) Novel approach to in-vivo oesophageal regeneration. in Lancet (London, England)

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Birchall M (2012) Tissue-engineered vascular replacements for children. in Lancet (London, England)

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Birchall MA (2012) Laryngeal transplantation in minipigs: early immunological outcomes. in Clinical and experimental immunology


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Birchall MA (2014) Tissue engineering's green shoots of disruptive innovation. in Lancet (London, England)


 
Description Advisor to house of Commons Select Committee on Regenerative Medicine, October 2016
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
 
Description One of only four regenerative medicine technologies highlighted in '8 Great Technologies' by DTI
Geographic Reach Europe 
Policy Influence Type Gave evidence to a government review
Impact Resulted in further citation as exemplar by MHRA for improvements in ATMP regulations at EME.
 
Description Clinical Research Training Fellowship (N. Hamilton)
Amount £260,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 01/2013 
End 06/2017
 
Description Sparks/MRC Clinical Training Fellowship (J.Fishman)
Amount £220,000 (GBP)
Organisation Sparks 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 01/2012 
End 01/2015
 
Description TETRA H20:20
Amount € 455,118 (EUR)
Funding ID 681027 
Organisation European Commission (EC) 
Department Horizon 2020
Sector Public
Country European Union (EU)
Start 01/2016 
End 01/2020
 
Description Technology Strategy Board Regenerative Medicine Call
Amount £2,400,000 (GBP)
Organisation Technology Strategy Board (TSB) 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 01/2014 
End 01/2018
 
Description Training Fellowship
Amount £280,000 (GBP)
Organisation The Wellcome Trust Ltd 
Department Wellcome Trust Bloomsbury Centre; Wellcome Trust
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 10/2013 
End 09/2016
 
Description Training Fellowship
Amount £280,000 (GBP)
Organisation The Wellcome Trust Ltd 
Department Wellcome Trust Bloomsbury Centre; Wellcome Trust
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 06/2016 
End 05/2019
 
Description UK SCF Open Call
Amount £750,000 (GBP)
Organisation UK Stem Cell Foundation 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 01/2013 
End 01/2017
 
Title Laryngeal bioreactor 
Description Bioreactor for preparation and transport of tissue engineered laryngeal implants 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact Improved speed, efficiency and sterility of implant preparation and transport 
 
Title Tissue engineered laryngeal mucosal sheet 
Description Serum and animal-derived feeder layer-free epithelial sheets for use clinically or as a screening tool for therapeutics and animal replacement. 
Type Of Material Model of mechanisms or symptoms - human 
Provided To Others? No  
Impact Rapid regeneration of laryngeal mucosa after injury; basis for a CASE studentship for near-human 3D laryngeal model 
 
Description Development of engineered respiratory mucosa 
Organisation University of Sheffield
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Clinical need, preclinical and clinical trial development, development of respiratory epithelial cell culture and bioreactor technologies
Collaborator Contribution Provision of buccal mucosa-derived epithelial sheet know-how
Impact Systematic review of mucosal engineering; contributed to success in gaining DPFS funding for laryngeal bioengineering clinical trial.
Start Year 2012
 
Description Novel hydrogels for respiratory epithelial delivery 
Organisation UK Regenerative Medicine Platform
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Clinical and scientific need, ability to translate into preclinical and clinical studies.
Collaborator Contribution Supply of novel hydrogels and other materials
Impact Just commenced
Start Year 2013
 
Description Research projects 
Organisation University College London (UCL)
Department evidENT (Evidence based ENT)
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution We provide clinical and scientific expertise to joint research projects dedicated to improving the lives of patients with ENT disorders.
Collaborator Contribution My partners in evidENT provide a large team of clinical, qualitative and quantitative researchers dedicated to developing and implementing evidence based practice for ENT in UK.
Impact NIHR grant for VOCALIST research project.
Start Year 2011
 
Description UK Regenerative Medicine Platform for Acellular Materials external advisor 
Organisation UKRMP Acellular Hub and UKRMP Immunomodulation Hub (Delcassian)
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution I am part of the external advisory group, and have specific oversight of clinical translation.
Collaborator Contribution Development of a number of novel materials and gels for therapeutic application
Impact Application for renewal funding
Start Year 2014
 
Description commercialisation of stem cell based airway products 
Organisation Cell Therapy Catapult
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution All academic input and IP
Collaborator Contribution Clinical trial and commercialisation support costs
Impact Successful TSB award for phase I clinical trial
Start Year 2013
 
Title Stem cell based tissue engineered laryngeal implant 
Description MRC funded phase I/II clinical trial 
Type Therapeutic Intervention - Surgery
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2013
Development Status Under active development/distribution
Clinical Trial? Yes
UKCRN/ISCTN Identifier NCT01977911
Impact First ever clinical trial of a stem cell based organ replacement 
URL http://clinicaltrials.gov/show/NCT01977911
 
Description Body of Songs 
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 Worked with a musician to record images of his larynx while he was singing. this was part of a larger project involving other musicans/artists and specialist clinicians.
Year(s) Of Engagement Activity 2015
URL http://bodyofsongs.co.uk/
 
Description Brighton Science Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact The audience showed great enthusiasm after the talk, asking questions and asking for further information.

Some young people who attended the festival were in touch following the talk, interested in coming to see my work.
Year(s) Of Engagement Activity 2013
 
Description Cheltenham Science Festival regenerative medicine showcase 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact 100 paying public participants; >400,000 hits for on-line webcast

Invited to develop further for Brighton Science Festival and Warwick TED-X talk, March, 2014; invited to speak to a variety of secondary school audiences nationally.
Year(s) Of Engagement Activity 2013
 
Description TEDX Warwick talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact My presentation provoked great interest and many questions followed. I have since been in touch with fellow presenters with potential for possible projects related to the voice.

The audience was very receptive to my talk and I have been contacted since then to do more presentations and attend more events.
Year(s) Of Engagement Activity 2013