Generating novel sources of stem cells for regenerative and anti-infective applications

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Bacterial resistance to antibiotics is well recognised as a major threat to animal and human health and there is an urgent need to find alternatives to the generalized use of antibiotics. The aim of this project is to develop robust approaches for the application of mesenchymal stem/stromal cell (MSC) preparations, and their products (e.g. exosomes) as cell-free off-the-shelf products, for tissue regeneration applications, including as anti-infectives and to combat antimicrobial resistance (AMR). Recent work [1,2], including from our laboratory [3], showed that MSCs and their conditioned media (CM/exosomes) can be used in the treatment of infection not only in animals, in multiple-drug resistant bacteria (MDR) in dogs and clinical bovine mastitis, but also in humans to treat GvHD, ARDS and Covid-19, and MDR tuberculosis. This project will aim to produce exosome cell-free-preparations from relevant large animal models towards the elucidation of the mechanisms underpinning MSCs regeneration and anti-microbial properties, and with a view to develop novel therapeutic cell-free products. This investigation may also lead to the identification of novel MSC-derived factors which could provide advantages as cell-free therapeutic products compared to current available commercially MSC therapies.References1. Leng Z, et al. (2020). Transplantation of ACE2(-) Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis 11:216-228.2. Johnson V, et al. (2017). Activated Mesenchymal Stem Cells Interact with Antibiotics and Host Innate Immune Responses to Control Chronic Bacterial Infections. Sci Rep 7:9575.3. Cortes-Araya Y, et al. (2018). Comparison of Antibacterial and Immunological Properties of Mesenchymal Stem/Stromal Cells from Equine Bone Marrow, Endometrium, and Adipose Tissue. Stem Cells Dev 27:1518-1525.