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Defining Feline Adipose-Derived Mesenchymal Stem Cells-Induced Alterations on T-lymphocytes and Implications for the Treatment of Viral and Inflammatory Conditions


Feline adipose-derived mesenchymal stem cells (ASCs) engage with a variety of immune cells and have been used in clinical trials for the treatment of inflammatory and immune-dysregulated diseases with notable success in feline chronic gingivostomatitis (FCGS). FCGS is a chronic, inflammatory oral disease, secondary to hyperactive immune response with strong causal association with feline calcivirus (FCV). However, the mechanisms by which feline ASCs modulate T-cells and their implementation in virus-associated conditions have been less explored. We showed that feline ASCs limit T-cell proliferation by causing G0-G1 cell cycle arrest, using the soluble mediator prostaglandin E2 (PGE2) and I-CAM 1/LFA-1 ligand interaction. Additionally, Feline ASCs also shift CD8+ T-cells’ phenotype toward terminally differentiated effector cells (CD57+, CD45R+, CD62L-) and upregulated granzyme B, IL-2 and KLRG-1 expression, enhancing their cytotoxic potential. Moreover, FCGS patients post-ASC therapy, had decreased level of T-cell activation in circulation and a lowered central memory CD8+ T-cell (TCM) in lymphoid tissue, possibly indicative of resolved chronic antiviral response. Feline ASCs could aid in disease cure caused by an underlying persistent viral infection.

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