Feline Foamy Virus Adversely Affects Feline Mesenchymal Stem Cell Culture and Expansion

Implications for Animal Model Development

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)814-823
Number of pages10
JournalStem Cells and Development
Volume24
Issue number7
DOIs
StatePublished - Apr 1 2015

Fingerprint

Spumavirus
Felidae
Mesenchymal Stromal Cells
Animal Models
Cell Culture Techniques
Tenofovir
Cell- and Tissue-Based Therapy
Mouth Diseases
Cats
Specific Pathogen-Free Organisms
Animal Disease Models
Cell Line
Therapeutic Uses
Virus Diseases
Giant Cells
Retroviridae
Transmission Electron Microscopy
Fats
Cell Proliferation
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

Cite this

@article{fe8f85dc83cd43b88980575dcc86dd61,
title = "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.",
author = "Boaz Arzi and Amir Kol and Murphy, {Brian G} and Walker, {Naomi J.} and Joshua Wood and Kaitlin Clark and Verstraete, {Frank J} and Borjesson, {Dori L}",
year = "2015",
month = "4",
day = "1",
doi = "10.1089/scd.2014.0317",
language = "English (US)",
volume = "24",
pages = "814--823",
journal = "Stem Cells and Development",
issn = "1547-3287",
publisher = "Mary Ann Liebert Inc.",
number = "7",

}

TY - JOUR

T1 - Feline Foamy Virus Adversely Affects Feline Mesenchymal Stem Cell Culture and Expansion

T2 - Implications for Animal Model Development

AU - Arzi, Boaz

AU - Kol, Amir

AU - Murphy, Brian G

AU - Walker, Naomi J.

AU - Wood, Joshua

AU - Clark, Kaitlin

AU - Verstraete, Frank J

AU - Borjesson, Dori L

PY - 2015/4/1

Y1 - 2015/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84925245474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925245474&partnerID=8YFLogxK

U2 - 10.1089/scd.2014.0317

DO - 10.1089/scd.2014.0317

M3 - Article

VL - 24

SP - 814

EP - 823

JO - Stem Cells and Development

JF - Stem Cells and Development

SN - 1547-3287

IS - 7

ER -