The effects of Interleukin-1 primed mesenchymal stem cells on hypoxic-ischemic brain damage

About the Project

Stroke is a leading cause of death and disability worldwide but with limited therapies, thus new therapeutic strategies are urgently needed. Inflammation after stroke is associated with poor outcome and is thus an attractive therapeutic target. A key mediator of inflammation is the cytokine interleukin-1 (IL-1), and blocking IL-1 actions have shown promise for acute neuroprotection and recovery in preclinical stroke models, and is currently tested in stroke patients. A potential new approach in stroke therapy is the targeted application of human mesenchymal (stromal) stem cells (MSCs) that can exert potent anti-inflammatory, neuroprotective and regenerative actions. In vitro pre-treatment of MSCs by specific culture conditions and/or biological agents (also known as “preconditioning” or “priming”) can improve the survival, engraftment, immunosuppressive and paracrine properties of MSCs, therefore enhancing their regenerative capacity. The effect of MSC priming with inflammatory mediators and hypoxia is unexplored, but our previous research found that MSCs can be primed by IL-1 and hypoxia to exert potent anti-inflammatory and neurotrophic effects in vitro. We have recently tested the beneficial effects of IL-1 preconditioning of MSCs in clinically-relevant animal stroke models for their potential use in future stroke therapies. We now aim to understand the mechanisms underlying those effects, and this project will study the effects of IL-1/hypoxia primed MSCs on neuroprotection in experimental stroke models, as well as neurones, endothelial cells and astrocytes injury after oxygen and glucose deprivation (OGD), with the ultimate aim to explore the potential clinical application of IL-1 primed MSCs in stroke.

Candidates are expected to hold (or be about to obtain) a minimum 2:1 Bachelors Degree with Honours (or equivalent) in Neuroscience or Biomedical Sciences. Research experience in cell cultures, in vivo animal models of disease and basic analytical techniques is desirable.

Eligibility

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

To be considered for this project you MUST submit a formal online application form – on the application form select PhD Neuroscience Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester

If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester)

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 (high) fee. Details of our different fee bands can be found on our website View Website