Assessment of effectiveness and safety of repeat administration of proinflammatory primed allogeneic mesenchymal stem cells in an equine model of chemically induced osteoarthritis
Barrachina, Laura (Universidad de Zaragoza. Servicio de Cirugía y Medicina Equina)
Remacha, Ana Rosa (Universidad de Zaragoza. Instituto Agroalimentario de Aragón)
Romero, Antonio (Universidad de Zaragoza. Servicio de Cirugía y Medicina Equina)
Vitoria, Arantza (Universidad de Zaragoza. Servicio de Cirugía y Medicina Equina)
Albareda, Jorge (Hospital Clínico Universitario "Lozano Blesa" de Zaragoza)
Prades, Marta (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Roca, Mercedes (Clínica Doctora Roca Diagnóstico Médico)
Zaragoza, Pilar (Universidad de Zaragoza. Instituto Agroalimentario de Aragón)
Vázquez, Francisco José (Universidad de Zaragoza. Servicio de Cirugía y Medicina Equina)
Rodellar, Clementina (Universidad de Zaragoza. Instituto Agroalimentario de Aragón)

Data:	2018
Resum:	This study aimed at assessing the effectiveness and safety of repeated administrations of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) primed with tumor necrosis factor (TNF)-α and interferon-γ in an equine model of chemically-induced osteoarthritis. Arthritis was induced in both radio-carpal (RC)-joints by amphotericin-B in 18 ponies, divided into three groups depending on the treatment injected: MSC-naïve (n = 7), MSC-primed (n = 7) and control (n = 4). The study consisted of two phases and used one RC-joint of each animal in each phase, with four months time-lapse, in order to assess two end-points. Clinical, synovial, radiological and ultrasonographic follow-up was performed. At six months, animals were euthanized and both carpi were assessed by magnetic resonance imaging (MRI), gross anatomy, histopathology, histochemistry and gene expression. Clinical and synovial inflammatory signs were quicker reduced in MSC-treated groups and repeated allogeneic administration did not produce adverse reactions, but MSC-primed group showed slight and transient local inflammation after second injection. Radiology and MRI did not show significant differences between treated and control groups, whereas ultrasonography suggested reduced synovial effusion in MSC-treated groups. Both MSC-treated groups showed enhanced cartilage gross appearance at two compared to six months (MSC-naïve, p < 0. 05). Cartilage histopathology did not reveal differences but histochemistry suggested delayed progression of proteoglycan loss in MSC-treated groups. Synovium histopathology indicated decreased inflammation (p < 0. 01) in MSC-primed and MSC-naïve at two and six months, respectively. At two months, cartilage from MSC-primed group significantly (p < 0. 05) upregulated collagen type II (COL2A1) and transforming growth factor (TGF)-β1 and downregulated cyclooxygenase-2 and interleukin (IL)-1β. At six months, MSC-treatments significantly downregulated TNFα (p < 0. 05), plus MSC-primed upregulated (p < 0. 05) COL2A1, aggrecan, cartilage oligomeric protein, tissue inhibitor of metalloproteinases-2 and TGF-β1. In synovium, both MSC-treatments decreased (p < 0. 01) matrix metalloproteinase-13 expression at two months and MSC-primed also downregulated TNFα (p < 0. 05) and IL-1β (p < 0. 01). Both MSC-treatments provided beneficial effects, mostly observed at short-term. Despite no huge differences between MSC-treatments, the findings suggested enhanced anti-inflammatory and regulatory potential of MSC-primed. While further research is needed to better understand these effects and clarify immunogenicity implications, these findings contribute to enlarge the knowledge about MSC therapeutics and how they could be influenced. The online version of this article (10. 1186/s12917-018-1556-3) contains supplementary material, which is available to authorized users.
Ajuts:	Ministerio de Economía y Competitividad AGL2011-28609
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cartilage ; Horse ; Joint pathology ; Immunogenicity ; Immunomodulation ; Synovial fluid
Publicat a:	BMC veterinary research, Vol. 14 (august 2018) , ISSN 1746-6148

DOI: 10.1186/s12917-018-1556-3
PMID: 30119668

17 p, 5.8 MB

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