Human and feline adipose-derived mesenchymal stem cells have comparable immunomodulatory functions

Adipose-derived mesenchymal stem cells (ASCs) are a promising cell therapy to treat inflammatory and immune-mediated diseases. Development of appropriate pre-clinical animal models is critical to determine safety and attain early efficacy data for the most promising therapeutic candidates. Naturally occurring diseases in cats already serve as valuable models to inform human clinical trials in oncologic, cardiovascular and genetic diseases. The objective of this study was to complete a comprehensive side-by-side comparison of human and feline ASCs with an emphasis on their immunomodulatory capacity and transcriptome. Similar to human ASCs, feline ASCs were highly proliferative at low passages and fit the minimal criteria of multipotent stem cells including a compatible surface protein phenotype, osteogenic capacity and normal karyotype. Like ASCs from all species, feline ASCs inhibited mitogen activated lymphocyte proliferation in vitro, with or without direct ASC-lymphocyte contact. Feline ASCs mimic human ASCs in their mediator secretion pattern including prostaglandin E2, indoleamine 2,3 dioxygenase, transforming growth factor beta and interleukin-6, all augmented by interferon gamma secretion by lymphocytes. The transcriptome of 3 unactivated feline ASC lines were highly similar. Functional analysis of the most highly expressed genes highlighted processes including: 1) the regulation of apoptosis, 2) cell adhesion, 3) response to oxidative stress, and 4) regulation of cell differentiation. Finally, feline ASCs had a similar gene expression profile to noninduced human ASCs. These data will help inform clinical trials using cats with naturally occurring diseases as surrogate models for human clinical trials in the regenerative medicine arena. Overall design: A total of 3 total RNA samples were analyzed in this study. The study included primary adipose-derived mesenchymal stem cell (MSC) cultures derived from 3 individual feline subjects: Gray Boy, Luna, and SPF2. The MSC cultures were cultured in standard tissue culture medium. At the desired density, total RNA was isolated and then submitted for RNA-sequencing analysis.

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Clark KC, Fierro FA, Ko EM, Walker NJ, Arzi B, Tepper CG, Dahlenburg H, Cicchetto A, Kol A, Marsh L, Murphy WJ, Fazel N, Borjesson DL