Feline Foamy Virus Adversely Affects Feline Mesenchymal Stem Cell Culture and Expansion: Implications for Animal Model Development

Abstract

Mesenchymal stem cells (MSCs) are a promising therapeutic option for various immune-mediated and inflammatory disorders due to their potent immunomodulatory and trophic properties. Naturally occurring diseases in large animal species may serve as surrogate animal models of human disease, as they may better reflect the complex genetic, environmental, and physiologic variation present in outbred populations. We work with naturally occurring diseases in large animal species to better understand how MSCs work and to facilitate optimal translation of MSC-based therapies. We are investigating the use of MSC therapy for a chronic oral inflammatory disease in cats. During our efforts to expand fat-derived feline MSCs (fMSCs), we observed that*50% of the cell lines developed giant foamy multinucleated cells in later passages. These morphologic alterations were associated with proliferation arrest. We hypothesized that the cytopathic effects were caused by infection with a retrovirus, feline foamy virus (FFV). Using transmission electron microscopy, polymerase chain reaction, and in vitro assays, we determined that syncytial cell formation and proliferation arrest in fMSCs were caused by FFV strains that were highly homologous to previously reported FFV strains. We determined that the antiretroviral drug, tenofovir, may be used to support ex vivo expansion and salvage of FFV-infected fMSC lines. MSC lines derived from specific pathogen-free cats do not appear to be infected with FFV and may be a source of allogeneic fMSCs for clinical application. FFV infection of fMSC lines may hinder large-scale expansion of autologous MSC for therapeutic use in feline patients.

Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats

“…Surface protein expression on fetal MSC lines was determined using flow cytometry, as described previously [17]. All antibodies were purchased from the Leukocyte Antigen Biology Laboratory, University of California, Davis (UCD), unless otherwise indicated.…”

Companion animals: Translational scientist’s new best friends

“…Because of these attributes, MSCs are currently in phase 1–3 clinical trials for immune-mediated diseases, and parallel clinical trials are ongoing at veterinary schools across the nation. We have proposed feline chronic gingivostomatitis as a naturally occurring disease model of human chronic oral inflammatory diseases (including oral lichen planus, stomatitis, oral Crohn’s disease, and pemphigus) (40, 41). This prevalent naturally occurring disease permits optimization of cell dose, route of administration, and cell source, all of which can inform human clinical trials.…”

Therapeutic Efficacy of Fresh, Allogeneic Mesenchymal Stem Cells for Severe Refractory Feline Chronic Gingivostomatitis

“…MSCs can inhibit T-cell proliferation, alter B-cell function, downregulate MHC II on antigen presenting cells and inhibit dendritic cell maturation and differentiation [22][23][24][25]. ASCs have been isolated and characterized in several species including humans [26][27][28][29][30][31][32].…”