Inflammation affects the viability and plasticity of equine mesenchymal stem cells: possible implications in intra-articular treatments.
Mesenchymal stem cells (MSCs) are gaining relevance for treating equine joint injuries because of their ability to limit inflammation and stimulate regeneration. Because inflammation activates MSC immunoregulatory function, proinflammatory priming could improve MSC efficacy. However, inflammatory molecules present in synovial fluid or added to the culture medium might have deleterious effects on MSCs. Therefore, this study was conducted to investigate the effects of inflammatory synovial fluid and proinflammatory cytokines priming on viability and plasticity of equine MSCs. Equine bone marrow derived MSCs (eBM-MSCs) from three animals were cultured for 72 h in media supplemented with: 20% inflammatory synovial fluid (SF); 50 ng/mL IFN-γ and TNF-α (CK50); and 20 ng/mL IFN-γ and TNF-α (CK20). Proliferation assay and expression of proliferation and apoptosis-related genes showed that SF exposed-eBM-MSCs maintained their viability, whereas the viability of CK primed-eBM-MSCs was significantly impaired. Tri-lineage differentiation assay revealed that exposure to inflammatory synovial fluid did not alter eBM-MSCs differentiation potential; however, eBM-MSCs primed with cytokines did not display osteogenic, adipogenic or chondrogenic phenotype. The inflammatory synovial environment is well tolerated by eBM-MSCs, whereas cytokine priming negatively affects the viability and differentiation abilities of eBM-MSCs, which might limit theirin vivoefficacy.
Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.|Service of Equine Surgery and Medicine, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
Laura
L
Barrachina
Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
Ana Rosa
AR
Remacha
Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.|Service of Equine Surgery and Medicine, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
Antonio
A
Romero
Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.|Service of Equine Surgery and Medicine, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
Francisco José
FJ
Vázquez
Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.|Service of Orthopedic Surgery and Traumatology, University Clinical Hospital Lozano Blesa, 50009 Zaragoza, Spain.
Jorge
J
Albareda
Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.|Service of Equine Surgery, Veterinary Hospital, Autonomous University of Barcelona, 08193 Barcelona, Spain.
Marta
M
Prades
Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
Beatriz
B
Ranera
Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
Pilar
P
Zaragoza
Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
Inmaculada
I
Martín-Burriel
Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
Clementina
C
Rodellar
D000818:Animals; D006734:Horse Diseases / Q000276:immunology* / Q000378:metabolism; D006736:Horses; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*; D007270:Injections, Intra-Articular / Q000662:veterinary; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D013582:Synovial Fluid / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
horses; joint diseases; mesenchymal stromal cells; proinflammatory cytokines; synovial fluid