Role of stem cell-derived extracellular vesicles in immune cell function; clinical development of a new biotherapeutic

About the Project

Lead supervisor:Prof Paul Genever

Co-supervisors:Dr Ioannis Kourtzelis

The student will be registered with the Department of Biology

Project overview

Human mesenchymal stem cells (MSCs) are found in adult tissues such as bone marrow and are able to form bone, cartilage and fat tissues. There is intense interest in determining how MSCs may be used in future cell-based therapies. However, little is known about MSC identity and research is often performed on heterogeneous mixtures of different MSC sub-populations. Using a process of telomerase-based immortalisation and cell cloning, we have generated several different MSC lines that represent different “types” of MSCs. We have identified MSC subtypes that have potent tissue regeneration capacity and others that do not differentiate but are immuno-suppressive. These functional differences are reflected in the products they secrete, including extracellular vesicles (EVs).

EVs are nano-sized, membrane-bound carriers of proteins and nucleic acids produced and released by cells that mediate intercellular communication. There is increasing evidence that EVs produced by MSCs can deliver many of the reparative and anti-inflammatory therapeutic benefits of the parent cells but with far fewer safety, delivery and cost limitations. EVs survive in the body for long periods without degrading or aggregating, they are acellular so present minimal risk of immunogenicity and they can be engineered to carry additional cargo, including pharmaceuticals. Consequently, there is huge interest in the development of EVs as a new therapeutic modality that combines the potency of stem cell therapies with the practicality of a biopharmaceutical. As our MSC parent lines are immortalised, we have a real opportunity to develop scaled-up procedures all the way to clinical translation. In addition, we have found one particular MSC line that produces highly bioactive EVs that could be used to treat inflammatory and degenerative disorders.

Key objectives

In this project, you will examine the characteristics of the MSC parent cell line and identify how their specialised EVs may be developed for clinical use. In particular, you will examine EV mechanism of action focusing on downstream intracellular signalling pathways, target cell interactions and immune cell-mediated responses. You will develop and validate macrophage polarisation and phagocytosis assays to assess whether these EVs can shift macrophages, a key immune cell type, from a pro-inflammatory state to an anti-inflammatory, tissue-repairing state. This is a fundamental mechanism that could underpin the EVs’ ability to resolve chronic inflammation and promote tissue regeneration. Techniques and skills training

Techniques will include sophisticated nano-analytical methods, phosphoprotein detection, flow cytometry, live cell imaging and co-culture assays. You will also perform important preclinical tests to identify appropriate disease targets.

The supervisory team

This is a truly exciting project that has the real potential to advance EV-based therapies all the way to the patient. There is an excellent supervisory team combining the Department of Biology, Hull York Medical School and York Biomedical Research Institute with access to world-class facilities to host your PhD in the beautiful and historic City of York.

The University of York is committed to recruiting future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and we have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

The Department of Biology holds an Athena SWAN Gold Award. We are committed to supporting equality and diversity and strive to provide a positive working environment for all staff and students.

Entry Requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with any biological, chemical, and/or physical science backgrounds, or students with mathematical background who are interested in using their skills in addressing biological questions.

Programme: PhD in Biomedical Science (3 year)

Start Date: 21 September 2026

Funding Notes

Students need to have adequate funds to cover 3 years of tuition fees and living expenses.