Feline Mesenchymal Stem Cells: What's Known and What's Possible
Dr. Pendergrass received her DVM degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory Universitys Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner ofJPen Communications, a medical communications company.
What is known about feline mesenchymal stem cell biology and immunology? We highlight studies that evaluated the cells’ therapeutic potential in cats.
Since their initial isolation and characterization from bone marrow in 2002, feline mesenchymal stem cells (MSCs) have been isolated from fat and fetal fluid. Because adipose-derived MSCs (aMSCs) are simple to obtain and proliferate easily, they have been used commonly to evaluate potential clinical applications.
For a recent review paper, Jessica M. Quimby, DVM, PhD, DACVIM, associate professor of internal medicine in the Department of Veterinary Clinical Sciences at The Ohio State University in Columbus, and Dori L. Borjesson, BA, DVM, MPVM, PhD, professor of pathology, microbiology, and immunology at the University of California, Davis, School of Veterinary Medicine, described what is known about feline MSC biology and immunology and highlighted studies that evaluated the cells’ therapeutic potential in cats.
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Biology and Immunology
Feline MSCs resemble fibroblasts and express the cell surface antigens CD44 (involved in cell—cell interactions and cell adhesion) and CD105 (vascular development and remodeling). Biological functions of feline MSCs include enhanced angiogenesis, tissue generation and repair, and inhibition of fibrosis in damaged organs.
Up to 80% of cats have feline foamy virus, which can infect up to 50% of feline MSC lines, ultimately causing cell death. These infected MSC lines can limit in vitro expansion and clinical application in cats.
The immunomodulatory properties of feline MSCs include downregulation of T-cell activity, reduced production of reactive oxygen species by neutrophils, and gene expression upregulation of numerous immunomodulatory mediators. Feline MSCs share many biological and immunologic functions with human, equine, and canine MSCs.
Feline MSCs’ immunomodulatory properties suggest therapeutic potential for inflammatory, immune-mediated, and degenerative feline diseases. Studies evaluating this possibility have used autologous and allogeneic MSCs and tested variations of other associated factors, including cell dose and administration route. Variable overall efficacy warrants the need for an optimal combination of MSC-associated factors for clinical use, the authors noted.
Feline Chronic Gingivostomatitis
Feline MSCs’ ability to downregulate T-cell activation could provide therapeutic benefit for feline chronic gingivostomatitis (FCGS), a debilitating disease with lesions characterized by a predominance of T and B cells. Investigators who administered autologous or allogeneic aMSCs intravenously in cats with FCGS reported a marked clinical improvement and even cure. The autologous aMSCs may be more effective, the authors noted.
Feline asthma treatment involves lifelong bronchodilator and corticosteroid therapy with no guarantee of adequate disease management. Notably, MSCs administered intravenously can reach the lungs, easing airway inflammation. The results of several pilot studies evaluating this approach for induced feline asthma showed markedly reduced airway eosinophilia and hyperresponsiveness for acute asthma and decreased airway remodeling for acute and chronic asthma.
Current treatments for chronic enteropathies (dietary management and corticosteroids) do not lead to satisfying clinical responses. Intravenous (IV) administration of aMSCs to cats with chronic enteropathies reportedly improved clinical outcome with few adverse events.
Early studies of MSCs for chronic kidney disease (CKD) treatment determined that intrarenal administration is not clinically practical, and sufficiently expanding autologous MSCs from elderly diseased cats is ultimately unrewarding. IV administration of allogeneic aMSCs in cats with CKD produced variable efficacy. “At this time,” the authors noted, “MSC therapy for feline CKD should be considered an experimental and unproven therapy.”
Treatment with aMSCs also has been evaluated for acute kidney injury, but results did not indicate improvement with aMSC administration.
Dr. Pendergrass received her doctor of veterinary medicine degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.