Identification of novel routes to modulate GMSC function to promote repair of gingival tissue

Lead Research Organisation: King's College London
Department Name: Craniofacial Dev and Stem Cell Biology

Abstract

The aim of this work proposed here is to characterise gingival mesenchymal stem cells derived from healthy and inflamed gingival tissue. Cell 'stemness' will be confirmed by performing colony forming assays and by examining multi-differentiation potential, including the ability of the cells to differentiate into gingival tissue. Studies comparing gene and protein expression of stem cells derived from healthy and inflamed tissue will also be carried out, with the aim of identifying 'healthy' and 'inflamed' gingival stem cell markers and to identify pathways and networks involved. The responses of 'healthy' and 'diseased' GMSCs exposed to inflammatory triggers will also be examined and it will be determined if these responses can be modulated using inhibitors and/or activators of the key pathways identified.

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/P504506/1 01/10/2016 30/03/2021
1820601 Studentship BB/P504506/1 01/11/2016 30/03/2021
 
Title Heads up! Shining a light on innovations in oral health 
Description This was an experimental arts-based programme that aimed to bring new perspectives to the Faculty of Dentistry, Oral & Craniofacial Sciences and our mission to understand disease, enhance health and restore function. Two artworks from this award contributed to this exhibition. Firstly, a collage art work of fluorescent tissue images; and a series of photographs showing materials used in this project. 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2019 
Impact It served to showcase how art and science collaborations can illuminate the lived experiences of patients and clinicians, bring new perspectives to researchers, and offer innovative approaches to student education. 
URL https://www.kcl.ac.uk/events/heads-up-shining-a-light-on-innovations-in-oral-health
 
Description Gingival mesenchymal cells are known to maintain the structural integrity of connective tissues by secreting the protein collagen and other components of the material that comprises the extracellular matrix. Additionally, their influence extends to modulating immunity and inflammation. The extent of heterogeneity within the oral mesenchyme and how specific cell types are affected during the course of disease progression are two questions that we aim to investigate in this project. To address these, we have characterised tissue specific gingiva mesenchymal cell populations to understand the mechanisms that regulate their activation using single cell RNA sequencing. We collected fresh gingival tissue biopsies from healthy and periodontitis affected subjects. Single-cell profiling of over 14,200 gingival cells reveals a striking dysregulation of the mesenchymal niche in disease with a decrease in functional populations that are linked to the aetiology of the disease. We also show divergent transcriptional regulators and functional pathways between health and disease. Our work provides a framework to interrogate human oral disease. Understanding the mechanisms regulating these processes holds promise to further our knowledge on tissue regeneration through the development of novel therapeutic strategies.
Exploitation Route The comprehensive data generated by this award will provide an extensive framework for the development of further studies. Whilst, we have focused on stromal cell types, we also generated data for other important cell identities important in disease pathogenesis that will require further understanding. Additionally, the methodology developed by this project can be used for the integration of further subjects in future projects.
Sectors Education,Healthcare,Pharmaceuticals and Medical Biotechnology
 
Description Machine Learning Training
Amount £480 (GBP)
Funding ID LIDO-03-22 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2022 
End 02/2022
 
Title Mapping the Spatial Dynamics of the Human Oral Mucosa in Chronic Inflammatory Disease 
Description Spatial transcriptomics datasets from human healthy and periodontitis affected oral mucosa samples. 
Type Of Material Database/Collection of data 
Year Produced 2023 
Provided To Others? Yes  
Impact These data is publicly available allowing other research groups to perform further analyses and generate novel hypotheses. 
URL https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE206621
 
Title Transcriptomic profiling of human gingiva in health and disease 
Description sc-RNAseq performed on gingival tissue isolated from healthy and periodontitis patients. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact Raw data allowed other research groups to generate novel hypotheses and to perform new analyses. These data have been integrated with other similar datasets for a future publication. 
URL https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE152042
 
Description Oral & Craniofacial Human Cell Atlas 
Organisation Queen Mary University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution This collaboration resulted in one publication and the establishment of the Oral & Craniofacial Human Cell Atlas.
Collaborator Contribution Research collaboration and participation in the Human Cell Atlas network.
Impact https://doi.org/10.1177/002203452211107
Start Year 2021
 
Description Arts in Dentistry workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact The Cultural Institute's Arts, Health and Wellbeing innovation programme explored how the arts can enhance health and wellbeing in clinical and care settings. The Arts in Dentistry strand offered opportunities for artists and arts organisations to develop new conversations and collaborations with Dental Institute researchers at King's College London. The aim was to conceive and develop experimental arts-based approaches to Understanding Disease, Enhancing Health and Restoring Function, with seed-funding being made available to the best ideas that emerge.
Year(s) Of Engagement Activity 2018