Arash Shahsavari, PhD Candidate, Thesis Review Seminar, "A pre-clinical trial using in vitro-derived mesenchymal stem cells to effect cartilage repair in a canine model of osteoarthritis"

Arash’s advisors are Dr Deanne Whitworth, Dr Dmitry Ovchinnikov, Prof Ernst Jurgen Wolvetang.

Research into stem cell-based therapeutics for human patients, particularly in the fields of regenerative medicine and immune-mediated and inflammatory disorders, continues to advance. Similarly, the demand for stem cell treatments for canine patients is increasing. In this seminar, I will discuss two studies, the first of which examines the potential anti-inflammatory and immunomodulatory properties of canine mesenchymal stem cells (MSCs). Human MSCs have been shown to possess potent anti-inflammatory and immunomodulatory properties. The invasive nature of MSC collection from adipose tissue or bone marrow, and the limited number of MSCs that can be isolated from the tissues, previously led to the development of a method of generating canine MSCs from induced pluripotent stem cells (iPSCs) in laboratory conditions. In this study, I examined the expression profile of anti-inflammatory and immunomodulatory cytokines in canine iPSC-derived MSCs (ciPSC.MSCs) in comparison with canine adipose tissue-derived MSCs (cAT.MSCs) and bone marrow-derived MSCs (cBM.MSCs) when stimulated with pro-inflammatory cytokines and in response to co-culture with mitogen-stimulated leukocytes. Results from this study support further investigation into the use of ciPSC.MSCs for the management of canine immune-mediated and inflammatory disorders. In the second study, I aimed to produce canine stem cells that were safe for clinical use. Although several lines of canine iPSCs exist, all were generated via techniques that require the integration of transgenes into the cells’ genome and so are not suitable for clinical applications. Thus, I have generated iPSCs from female adult dog BM.MSCs using a novel Sendai virus-mediated re-programming method that does not require transgene integration. Furthermore, our cells can be maintained in conditions that support the presence of two active X chromosomes and therefore a more naïve state of pluripotency, such as that found in cells of the inner cell mass of the embryo. Studies in mouse and human have shown that the state of pluripotency is an important consideration when modelling cellular functions and disease states; our data suggests that similar considerations of pluripotent state should be made when using canine pluripotent cells.

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