Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome.
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.



Human and feline ASCs were evaluated for phenotype, immunomodulatory profile, and transcriptome. Additionally, transwells were used to determine the role of cell-cell contact in ASC-mediated inhibition of lymphocyte proliferation in both humans and cats.



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 three 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.



Findings suggest that feline ASCs modulate lymphocyte proliferation using soluble mediators that mirror the human ASC secretion pattern. Uninduced feline ASCs have similar gene expression profiles to uninduced human ASCs, as revealed by transcriptome analysis. 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.
Veterinary Institute for Regenerative Cures and Department of Pathology, Microbiology and Immunology, University of California, Davis, CA, 95816, USA.
Kaitlin C
KC
Clark
Institute for Regenerative Cures and Department of Cell Biology and Human Anatomy, University of California, Davis, CA, 95816, USA.
Fernando A
FA
Fierro
Veterinary Institute for Regenerative Cures and Department of Pathology, Microbiology and Immunology, University of California, Davis, CA, 95816, USA.
Emily Mills
EM
Ko
Veterinary Institute for Regenerative Cures and Department of Pathology, Microbiology and Immunology, University of California, Davis, CA, 95816, USA.
Naomi J
NJ
Walker
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, 95816, USA.
Boaz
B
Arzi
Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, 95816, USA.
Clifford G
CG
Tepper
Institute for Regenerative Cures and Department of Cell Biology and Human Anatomy, University of California, Davis, CA, 95816, USA.
Heather
H
Dahlenburg
Institute for Regenerative Cures and Department of Cell Biology and Human Anatomy, University of California, Davis, CA, 95816, USA.
Andrew
A
Cicchetto
Veterinary Institute for Regenerative Cures and Department of Pathology, Microbiology and Immunology, University of California, Davis, CA, 95816, USA.
Amir
A
Kol
Veterinary Institute for Regenerative Cures and Department of Pathology, Microbiology and Immunology, University of California, Davis, CA, 95816, USA.
Lyndsey
L
Marsh
Department of Dermatology, School of Medicine, University of California, Davis, CA, 95816, USA.
William J
WJ
Murphy
Department of Dermatology, School of Medicine, University of California, Davis, CA, 95816, USA.
Nasim
N
Fazel
Veterinary Institute for Regenerative Cures and Department of Pathology, Microbiology and Immunology, University of California, Davis, CA, 95816, USA. dlborjesson@ucdavis.edu.
Dori L
DL
Borjesson
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002415:Cats; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D056747:Immunomodulation / Q000187:drug effects / Q000235:genetics*; D018836:Inflammation Mediators / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics*
D007155:Immunologic Factors; D018836:Inflammation Mediators; D008934:Mitogens
Adipose tissue; Animal model; Feline; Human; Immunomodulation; Mesenchymal stem cell; Multipotent adult progenitor cell