Transcriptome Analysis of the Umbilical Cord-Mesenchymal Stromal Cells’ Therapeutic Response to inflammation, with a view to banking the most potent Cells for Allogeneic Therapy

Claire Mennan, Helen McCarthy, Daniel Tonge & Sally Roberts

Funded by the Orthopaedic Institute and Versus Arthritis

Mesenchymal Stromal Cells (MSCs) isolated from bone marrow (BM) are considered to be the “gold standard” for MSC populations which can be used for cell therapy. However, sourcing them can be painful and provide limited numbers of cells. Umbilical Cords (UCs) show great potential as an alternative source of MSCs as they are normally thrown away and also UC-MSCs proliferate faster in culture than BM-MSCs, allowing larger numbers to be produced quicker which would be necessary for creating large numbers of allogeneic cells for treating greater numbers of patients. UC-derived MSCs also have an immune-privileged status and an immunomodulatory phenotype (meaning they are less likely to elicit an immune response when used in a person they were not sourced from), again making them attractive candidates for allogeneic cell based therapies. Previous work in our group has focussed on sourcing MSCs from whole UC and characterising the cells’ modulatory properties in an inflammatory environment, such as that which may be found in an inflamed joint. 

The International Society for Cell Therapy (ISCT) advises that characterisation of MSCs destined for cell therapy should include activation or ‘licensing’, which involves stimulation with inflammatory molecules such as interferon gamma (IFN-γ), either alone or with TNF-α. These molecules are often found in joints of patients with rheumatoid arthritis or osteoarthritis. The production of molecule such as indoleamine 2,3-dioxygenase (IDO), which are known to dampen down inflammation, only occurs following activation with these inflammatory cytokines.  We have found, however, that different peoples’ cells can respond differently in how much IDO they produce. This suggests that it would be important for cells destined for allogeneic cell banks to have their immunomodulatory potential tested prior to banking, to characterise the response to inflammatory cytokines for each donor. 

We are working on using state of the art RNA-sequencing of the transcriptome of UC-MSC donors with either high or low response to inflammatory cytokines (as assessed via IDO gene expression). This should help to identify the most potent cells for allogeneic cell therapy and cell banking.