Spinal cord repair from endogenous stem cells in the spinal niche

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biomedical Sciences

Abstract

Spinal cord injury in humans leads to permanent loss of function. This is despite the presence of
stem cell like cells in the spinal cord. In contrast, zebrafish regain full swimming capacity after a
lesion and their spinal stem cells make new neurons that contribute to the repair.

Here we plan to identify the signals acting on the stem cells in the fish to then use them to improve
the reaction of stem cells of humans (in a dish) and spinal cord repair in rat models. In the course
of the project, we will develop tools that will aid our research, but also contribute to the work of our
colleagues in the community: We will develop small proteins that can be used to drive stem cells
into a repair type, we will adapt a new microscopy technique to monitor repair in live fish and rats
as it happens, and we will develop new stem cell lines directly from human spinal cord material.

This project will identify repair factors that could then be taken into clinical trials. Our team
comprises colleagues from the UK, Germany, Belgium, France and Poland, among them basic
neuroscientists and neurosurgeons.

Technical Summary

We hypothesize that small differences in the environment of zebrafish and mammals spinal stem/progenitor cells determine regenerative success or failure. We need to characterize and compare the cellular diversity and differential properties of adult spinal cord stem cell niches in zebrafish, rodents and human. We will elucidate the molecular mechanisms controlling niche dormancy vs activation and stem cell fate after spinal cord injury, exploring why mammals spinal cord stem cell do not generate neurons after SCI. We will explore the human spinal cord stem cell niche and generate human spinal cord stem cell lines for further investigation of human niche cell properties. We aim to enhance functional repair after mammalian spinal cord injury by defining innovative tools (nanobodies) and identifying molecules to manipulate the activity and fate of spinal cord neural stem and progenitor cells after injury.

Planned Impact

This is a collaborative proposal generating a European consortium of researchers in the UK, Germany, France, Belgium, and Poland. Translation is a cornerstone of this project. It will generate significant knowledge on the mechanisms of endogenous spinal cord repair, functionally tested in an in vivo (rat) spinal cord model, with direct human validation (through expression and in vitro studies of human material/cells). Furthermore, valuable tools will be created which will drive innovation and
development of therapies.

We will train PhD students, postdocs, and MSc students, exposing them to the problem of spinal cord injury and the inability of mammals, including humans to repair damage to the spinal cord. This will hopefully lead to more young researchers entering the field.

Tools and findings from this research will be widely shared, increasing the likelihood of successful translation of the project's finding into therapies.

We will be running an active and wide public engagement programme increasing awareness of and support for spinal cord injury research and offering access to scientific thinking/concepts to pupils in schools/areas with poor access to such work.

Publications

10 25 50
 
Description Reaktivierung und Umprogrammierung spinaler Progenitorzellen zu regenerativer Neurogenese
Amount € 1,081,590 (EUR)
Funding ID Projektnummer 514187677 
Organisation German Research Foundation 
Sector Charity/Non Profit
Country Germany
Start 03/2023 
End 03/2026
 
Title Automated Laser Lesion 
Description Using the micropoint laser on our VAST Bioimager set up to automate spinal cord lesions in 3 day old zebrafish - presented at the Eranet Neuron midterm symposium in Bonn, January 2019 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Year Produced 2019 
Provided To Others? Yes  
Impact ongoing 
 
Description JP Hugnot 
Organisation University of Montpellier
Country France 
Sector Academic/University 
PI Contribution JP Hugnot is a member of the NEURONICHE consortium, we are exchanging data towards a research paper and have written a joint review (publication pending).
Collaborator Contribution data exchange
Impact joint review (accepted in principle, no DOI yet)
Start Year 2017
 
Description Horizons Neuroscience 2020 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Around 80 researchers and representatives from the pharmaceutical and biotech industries came together to seek innovation opportunities at the University of Edinburgh's Horizons in Neuroscience conference, hosted by EI.

The event aimed to ignite ideas in the fields of developmental, regenerative and degenerative neuroscience and to explore opportunities for translating research into commercial development.

The conference was opened by Professor Siddharthan Chandran, Director of Edinburgh Neuroscience, and Dr Andrea Taylor, EI's Head of Business Development for the University's College of Medicine and Veterinary Medicine (CMVM).
Year(s) Of Engagement Activity 2020
URL https://edinburgh-innovations.ed.ac.uk/2020/02/19/looking-to-the-horizon-in-neuroscience/