Humoral immune response against allogeneic equine mesenchymal stem cells (MSCs) mediated by the major histocompatibility complex (MHC): an issue to take into account for the safety and efficacy of treatment with MSCs

Cequier, A. (Universidad de Zaragoza) ; Barrachina, L. (Universidad de Zaragoza) ; Romero, A. (Universidad de Zaragoza) ; Vitoria, A. (Universidad de Zaragoza) ; Zaragoza, P. (Universidad de Zaragoza) ; Vazquez, F.J. (Universidad de Zaragoza) ; Rodellar, C. (Universidad de Zaragoza)

Resumen: Allogeneic mesenchymal stem cells (MSCs) present several advantages, but recipient immune response needs to be further elucidated. Proinflammatory priming of MSCs activated their in vivo regulatory capacity, but repeated administrations led to slight inflammatory reaction in an osteoarthritis equine model. This may be associated with higher major histocompatibility complex (MHC) expression, which would increase MSC immunogenicity potentially inducing humoral mediated immune memory. This study aimed at assessing allo-antibody production against donor’s equine MHC (equine leukocyte antigen, ELA) in animals that received intra-articular repeated administration of allogeneic MSC-primed. For this purpose, we used stored samples from a previous study. Donor and recipients ELA-haplotypes were stablished by microsatellite typing and complementmediated microcytoxicity assays were carried out by exposing target cells from the donor (unstimulated MSCs [MSC-nai¨ve], MSC-primed or lymphocytes [control]) to sera collected at different time-points from 10 recipients: ELA-mismatched MSCnai ¨ve recipients, ELA-mismatched MSC-primed recipients or ELA-partially matched MSC-primed recipients. All animals receiving allogeneic MSCs produced allo-antibodies after the first injection, regardless of the matching degree. However, antibody peak production after second administration was only observed in ELA-mismatched recipients, both of MSC-nai¨ve and MSCprimed. Horses injected with MSC-primed produced fewer antibodies but MSC-primed were more targeted in the microcytoxicity assay. Thus, activated immunomodulatory profile of MSC-primed could have led to slighter humoral response after ...

Idioma: Inglés

Año: 2019

Publicado en: HUMAN GENE THERAPY 30, 11 (2019), A164
ISSN: 1043-0342

Originalmente disponible en: Texto completo de la revista

Factor impacto JCR: 4.273 (2019)

Categ. JCR: BIOTECHNOLOGY & APPLIED MICROBIOLOGY rank: 30 / 156 = 0.192 (2019) - Q1 - T1
Categ. JCR: GENETICS & HEREDITY rank: 38 / 176 = 0.216 (2019) - Q1 - T1
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 40 / 138 = 0.29 (2019) - Q2 - T1

Factor impacto SCIMAGO: 1.648 - Genetics (Q1) - Molecular Medicine (Q1) - Molecular Biology (Q2)

Tipo y forma: Article (Published version)

Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Medicina y Cirugía Animal (Dpto. Patología Animal)