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Full NameProfessor Thomas Ritter
Organisation:National University of Ireland Galway
- infectious disease and the immune system
- cell and developmental biology/regenerative medicine
- bioengineering/medical devices
Other Research Fields:
Inflammatory disease of the eye, transplantation
Postgrad Medical Specialties
- Sports and Exercise Medicine
- Adolescent medicine
Millions of people worldwide suffer from sight-threatening inflammatory eye diseases while current treatment protocols are insufficient. My lab is interested in developing novel gene and cell therapeutic strategies for the treatment of inflammatory eye diseases. We have established a series of in vitro and in vivo potency assays to investigate this in great detail.
Currently we follow several lines of investigation to probe therapeutic efficacy and mechanism of action. These include:
To investigate whether the immunomodulatory properties of “immuno-enhanced” mesenchymal stem cells can be utilised to improve corneal allograft survival (eg Treacy et al., 2014)
To understand the mechanism of Programmed Death-Ligand 1 mediated promotion of corneal allograft survival (eg Nosov et al., 2012)
To understand how changes in cell surface glycosylation modulate the tolerogenic potential of regulatory cells including mesenchymal stem cells
To understand to role of extracellular vesicles secreted from mesenchymal stem cells in modulation of ocular surface injury (eg Rani et al., 2015 and Rani et al., in preparation)
To investigate whether the immunomodulatory properties of “immuno-enhanced” mesenchymal stem cells can be utilised to modulate intraocular inflammation (Uveitis)
Key words: Immunology, Transplantation, Mesenchymal Stem Cells, Immunomodulation, tolerogenic cells, Extracellular vesicles, Ocular surface injury, Gene Therapy
This project will investigate the therapeutic potential of “immune-enhanced” human mesenchymal stem cells (MSC) for intraocular inflammation and study the mechanism behind. The application of MSC has been shown to be safe and therapeutically efficacious in many different diseases such as Graft versus Host Disease, Cardiovascular Disease, Diabetes or Transplantation. Interestingly, the source of the MSC (allogeneic or autologous) seems to be important for therapeutic efficacy. We could show that allogeneic but not autologous MSC are therapeutically efficacious in a corneal transplant model (Treacy et al., 2014). However, allogeneic MSC may induce a recipient immune response and for many non-life threatening diseases it might be more desirable to use autologous MSC compared to allogeneic MSC. We have generated preliminary data using mouse MSC that shows pre-treatment of MSC with cytokines leads to “immune-enhanced” MSC with increased therapeutic efficacy in vitro and in vivo.
In this project we will utilise “immune-enhanced” human MSC from healthy donors to study the therapeutic effect in a mouse model of intraocular inflammation (LPS-induced Uveitis) and study the mechanism of action. Moreover, the potential of extracellular vesicles isolated from culture supernatants of “immune-enhanced” MSC will also be investigated with the view of future “cell-free” therapy. This project will lead to novel observations for therapeutic treatment of inflammatory eye disease and identify novel mechanisms of MSC-mediated immunomodulation. All technologies which will be utilised in this project are established in the lab which include MSC isolation and cell culture, “immune-enhancing” with cytokines, characterisation of MSC by flow cytometry, in vitro potency assays to test for immunomodulatory properties of “immune-enhanced” MSC such as ELISA, qPCR, mixed lymphocyte reaction, pre-clinical model, isolation of extracellular vesicles, histology, immunohistochemistry.