Mathematical Modelling of Magnetically Targeted Stem Cell Delivery

Lead Research Organisation: University of Oxford
Department Name: Mathematical Institute

Abstract

This project aims to develop mathematical models of a magnetically targeted stem cell delivery technique. The development of an effective method of targeting delivery of stem cells to the site of an injury is a key challenge in regenerative medicine. However, production of stem cells is costly and current delivery methods rely on large doses in order to be effective. Improved targeting through use of an external magnetic field to direct delivery of magnetically-tagged stem cells to the injury site would allow for smaller doses to be used. Developing an accurate mathematical model can reduce required amount of laboratory testing and allow this therapy to reach clinical testing stages faster.

The objective of this project is to create a detailed model of this regenerative medicine therapy containing the dominant features of the underlying continuum mechanics, electrodynamics and mathematical biology. The accuracy of the mathematical model can be verified against real data provided by our collaborators at the University of Birmingham. We aim to use our model in a predicative context to address safety issues critical to the success of the therapy; during experimentation stem cells were found to form dangerous clumps in the body. We will address this issue by including intercellular magnetic and biological forces, through which we aim to determine parameter regimes which offer lower risks of clumps of stem cells leaving the injury site and travelling in the blood system. Furthermore we aim to provide fast and cheap parameter exploration in order to optimise the costly experimental process.

This project will extend existing models to the case of targeting stem cells implanted with magnetic nanoparticles: the majority of models to date consider the case of magnetic nanoparticle transport alone. Secondly we will address the safety issue of clumping not considered for magnetically tagged stem cells, through realistic microscopic magnetic modelling of stem cells implanted with nanoparticles. We will additionally improve biological realism of models by inclusion of additional features of the vessels such as the geometry, through curvature, and the microscale wall structure through inclusion of the porous layer lining the vessels, the glycocalyx.

This project falls into the EPSRC research areas of Mathematical Sciences and Healthcare Technologies, since we aim to optimise a regenerative medicine therapy through the use of mathematical modelling. We are working in collaboration with Prof Alicia El Haj and Dr Hareklea Markides at the University of Birmingham who carry out this therapy in vitro and in vivo. This collaboration allows us to address questions which are relevant and important to the regenerative medicine community.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509711/1 30/09/2016 29/09/2021
2100104 Studentship EP/N509711/1 30/09/2018 29/06/2022 Edwina Yeo
EP/R513295/1 30/09/2018 29/09/2023
2100104 Studentship EP/R513295/1 30/09/2018 29/06/2022 Edwina Yeo
 
Description We have developed two mathematical models for aspects of magnetic drug delivery and related problems in vascular fluid mechanics. These have helped address open questions which biological scientists have about key processes in blood flow and about novel drug delivery techniques.
Exploitation Route This will help biological scientists design more effective experiments reducing the number of animal tests required.
Sectors Pharmaceuticals and Medical Biotechnology

 
Title Code for Magnetic cell delivery simulations 
Description Comsol and matlab simulation codes for the transport of stem cells in a channel which deforms as cells aggregate on vessel wall. Datasets for parameter analysis. 
Type Of Material Computer model/algorithm 
Year Produced 2020 
Provided To Others? Yes  
Impact Dataset and model was used for journal article, 'Experimental and mathematical modelling of magnetically labelled mesenchymal stromal cell delivery (2021) Author: E. Yeo, H. Markides, A.T. Schade, A.J. Studd, J.M. Oliver, S.L. Waters, A.J. El Haj, Royal Society Interface' 
URL https://github.com/Edwina-Yeo/Magnetic-Cell-Delivery-Simulations
 
Description Experimental-Modelling Collaboration - Technion 
Organisation Technion - Israel Institute of Technology
Country Israel 
Sector Academic/University 
PI Contribution Mathematical modelling of mechanisms of arterial clot formation.
Collaborator Contribution Insight into the biological application, experimental data to compare model outcomes to.
Impact This collaboration is multidiciplinary. We contribute mathematical modelling, our collaborators are based in biomedical engineering. We have developed a novel mathematical model through this collaboration.
Start Year 2019
 
Description Experimental-Modelling Collaboration - University of Birmingham 
Organisation University of Birmingham
Country United Kingdom 
Sector Academic/University 
PI Contribution We have developed mathematical models for experimental therapies developed by Professor Alicia El Haj's group at the University of Birmingham, Healthcare Technology Institute.
Collaborator Contribution Our collaborators provided insight into the biological application of our model, allowing us to construct relevant mathematical models. They also provided experimental data for us to compare model outputs on.
Impact This has resulted in multiple conference presentations and one publication. We have developed two novel mathematical models for this application. The collaboration is multidisciplinary: we delivery mathematical modelling and our partners are researching regenerative medicine.
Start Year 2018
 
Description 3 minute thesis competition 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Competition aimed at summarising your research to a wider audience.
Year(s) Of Engagement Activity 2021
 
Description Help at Graduate Open day for Research group 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact Personal discussions offered with applicants for graduate programs in my research group.
Year(s) Of Engagement Activity 2020
 
Description Oral Presentation at Americal Physical Society, Division of Fluid dynamics Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Online 10 minute recorded talk for virtual conference with drop in question time. Lead to discussions with other researchers and students.
Year(s) Of Engagement Activity 2020
URL https://ui.adsabs.harvard.edu/abs/2019APS..DFDM03032Y/abstract
 
Description Oral Presentation at Euromech, 'Fluid and solid mechanics for tissue engineering ' Colloqium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact 20 minute oral presentation to approximately 30 people. Lead to a new collaboration.
Year(s) Of Engagement Activity 2019
URL https://604.euromech.org/
 
Description Oral Presentation at Internal Department Seminar Series 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact 10 minute oral presentation at mathematics department seminar at the 'Oxford Centre for Applied Industrial Mathematics' with following questions.
Year(s) Of Engagement Activity 2020
URL https://www.maths.ox.ac.uk/node/37549
 
Description Oral Presentation at Junior Applied Mathematics Seminar Series 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Oral presentation on research, with a discussion afterwards ~15 people.
Year(s) Of Engagement Activity 2019
URL https://www.maths.ox.ac.uk/node/31813
 
Description Oral Presentation at Society for Mathematical Biology Annual Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact 20 Minute Oral presentation at a virtual conference, delivered live. With discussions afterwards.
Year(s) Of Engagement Activity 2020
URL https://smb2020.org/OTHE_Wednesday_MS1/
 
Description Outreach activity for school children 'I'm a scientist get me out of here' 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Online chat sessions with students about working as a scientist.~ 15 students per session.
Year(s) Of Engagement Activity 2019
URL https://hertford19.imascientist.org.uk/profile/edwinayeo/
 
Description Poster Presentation at Women in Mathematics Symposium ETH 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Poster presentation to study participants ~25 people.
Year(s) Of Engagement Activity 2019
URL https://math.ethz.ch/news-and-events/events/gomath/gomath-2019/symposium.html
 
Description Society for Industrial Applied Mathematics 3 minute Thesis competition presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact 3 minute talk summarising my research to a non technical audience.
Year(s) Of Engagement Activity 2021
URL https://www.maths.ox.ac.uk/node/38125
 
Description Talk at 'Mathematix' engagement session for undergraduates 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact Presentation on my research and life as a PhD students with approximately 10 students.
Year(s) Of Engagement Activity 2021
 
Description Talk at American Physical Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Oral presentation to approximately 20 people at Americal Physical Society with the following discussion with participants.
Year(s) Of Engagement Activity 2021
URL https://meetings.aps.org/Meeting/DFD21/Session/T15.10