Arzi B, Kol A, Murphy B, et al. Feline foamy virus adversely affects feline mesenchymal stem cell culture and expansion: implications for animal model development. Stem Cells Dev. 2015 Apr 1;24(7):814-23. (Winn-funded study)
Mesenchymal stem cells (MSCs) are being extensively evaluated as a potential therapy in different immune-mediated and inflammatory disorders. MSCs have potent immunomodulatory and trophic properties: inhibition of T-cell proliferation, altering B-cell function, downregulating major histocompatibility complex (MHC) II, and inhibition of dendritic maturation and differentiation. In this study, researchers decided to investigate MSC therapy for feline chronic gingivostomatitis (FCGS) which is a common, often painful immune-mediated oral mucosal disease in cats.
In the process of expanding fat-derived MSCs (fMSCs) they observed that 50% of the cell lines developed giant foamy multinucleated cells at later (3-5) stages of passage. The cell lines failed to proliferate. With this project, they demonstrated that a retrovirus, feline foamy virus (FFV), infection in the fMSCs posed a problem for long term culture and could affect the clinical application of autologous (self) MSCs in cats. One method of confirmation is that control cells maintained typical fMSC morphology throughout the study but all inoculated cultures contained many syncytial cells by 48 h after inoculation. They also found through electron microscopy, PCR, and in vitro assays that the proliferation arrest was caused by FFV strains similar to previously reported FFV strains. Clinical stem cell therapy requires the expansion of high numbers of cells to achieve the best effect.
The authors did look at different methods to bypass the adverse effects of FFV on fMSC culture and clinical application. It was noted that FFV may be found in 20-80% of cat cell lines. They found that the early addition of a reverse transcriptase inhibitor, tenofovir, to the fMSC culture media was effective in inhibiting these adverse effects of FFV infection in fMSCs. While FFV has no known pathologic consequences in cats, the potential adverse effects associated with readministration of actively replicating FFV to the recipient animal are currently unknown. Their recommendation is that each cat be screened for FFV before working with its MSCs (autologous stem cell therapy) and infection prevention measures are taken to protect other cell lines. (VT)