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

Abstract

Mesenchymal stem cells (MSCs) have potent immunomodulatory functions and are a promising therapy for immune‐mediated inflammatory disorders. We previously demonstrated the efficacy of fresh, autologous, adipose‐derived MSCs (ASCs) to treat feline chronic gingivostomatitis (FCGS), a chronic oral mucosal inflammatory disease similar to human oral lichen planus. Here, we investigate the use of fresh allogeneic ASCs for treatment of FCGS in seven cats. Radiolabeled ASCs were also tracked systemically. Each cat received two intravenous injections of 20 million ASCs, 1 month apart. Oral inflammation, blood lymphocyte subsets, anti‐fetal bovine serum antibody levels, ASC crossmatching and serum proteins and cytokine concentrations were determined. Four of the 7 cats (57%) responded to treatment [complete clinical remission (n = 2) or substantial clinical improvement (n = 2)]. Three cats were nonresponders. Prior to therapy, most cats had increased circulating CD8+ T cells, decreased CD8lo cells, and a decreased CD4/CD8 ratio, however clinical resolution was not associated with normalization of these parameters. Nonresponders showed more severe systemic inflammation (neutrophilia, hyperglobulinemia and increased interferon gamma and tumor necrosis factor alpha concentration) prior to ASC therapy. Clinical remission took up to 20 months and no clinical relapse has occurred. A higher fraction of radiolabeled ASCs were identified in the oral cavity of FCGS affected cats than the control cat. The administration of fresh, allogenic ASCs appeared to have lower clinical efficacy with a delayed response as compared to the fresh, autologous ASCs. In addition, the mechanism(s) of action for autologous and allogenic ASCs may differ in this model of oral inflammation. Stem Cells Translational Medicine 2017;6:1710–1722

Intra‐arterial renal infusion of autologous mesenchymal stem cells for treatment of chronic kidney disease in cats: Phase I clinical trial

“…Additional studies in which MSC are culture‐expanded, characterized, and administered at various doses are needed to more definitively associate study results with MSC alone as well as with MSC dose. Radiolabeling of MSC and tracking their migration with nuclear scintigraphy as recently has been done in cats and horses also could be considered to assess MSC engraftment in the kidney and association with clinical outcome, but renal clearance of the radiolabel may complicate the interpretation of results …”

“…Some of the specific challenges described above are avoided with 34,35 The source of adipose tissue used for SVF in our study varied among patients. Multiple studies in dogs and people have shown differences in MSC yield as well as replication rate and differentiation ability of MSC depending on the source of adipose tissue (eg, omental versus SC).…”

Isolation and Characterization of Feline Wharton’s Jelly-Derived Mesenchymal Stem Cells

“…Recent studies show that feline MSC has therapeutic effects of gingivostomatitis, asthma, chronic kidney disease, and enteritis in feline medicine. (16)(17)(18)(19). Feline MSC has been isolated from bone marrow, adipose tissue and amniotic membrane (11,20,21).…”

Session 10: Anaesthesia and Pain Control

“…These are species-specific Ab targeting NGF which has an important role in pro-nociception. In addition, recent research has indicated a potential efficacy of the use of autologous mesenchymal stem cell therapy for the treatment of severe refractory gingivostomatitis, an important cause of chronic pain in cats (8 Introduction/Objective: In several EU and some US states, medical marijuana is an option for people suffering from various ailments and seeking relief. As cannabis is now sold as an oil extract, it has become a conceivable option for dogs too.…”

“…These are species-specific Ab targeting NGF which has an important role in pro-nociception. In addition, recent research has indicated a potential efficacy of the use of autologous mesenchymal stem cell therapy for the treatment of severe refractory gingivostomatitis, an important cause of chronic pain in cats (8). stress and anxiety, arthritis and cancer pain, but no information on its pharmacokinetics is available in dogs.…”