Immune response to allogeneic equine mesenchymal stromal cells

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dc.citation.issue1
dc.citation.volume12
dc.contributor.authorKamm JL
dc.contributor.authorRiley CB
dc.contributor.authorParlane NA
dc.contributor.authorGee EK
dc.contributor.authorMcIlwraith CW
dc.coverage.spatialEngland
dc.date.accessioned2024-02-01T00:21:50Z
dc.date.accessioned2024-07-25T06:50:02Z
dc.date.available2021-11-12
dc.date.available2024-02-01T00:21:50Z
dc.date.available2024-07-25T06:50:02Z
dc.date.issued2021-12
dc.description.abstractBACKGROUND: Mesenchymal stromal cells (MSCs) are believed to be hypoimmunogeneic with potential use for allogeneic administration. METHODS: Bone marrow was harvested from Connemara (n = 1), Standardbred (n = 6), and Thoroughbred (n = 3) horses. MSCs were grouped by their level of expression of major histocompatibility factor II (MHC II). MSCs were then sub-grouped by those MSCs derived from universal blood donor horses. MSCs were isolated and cultured using media containing fetal bovine serum until adequate numbers were acquired. The MSCs were cultured in xenogen-free media for 48 h prior to use and during all assays. Autologous and allogeneic MSCs were then directly co-cultured with responder leukocytes from the Connemara horse in varying concentrations of MSCs to leukocytes (1:1, 1:10, and 1:100). MSCs were also cultured with complement present and heat-inactivated complement to determine whether complement alone would decrease MSC viability. MSCs underwent haplotyping of their equine leukocyte antigen (ELA) to determine whether the MHC factors were matched or mismatched between the donor MSCs and the responder leukocytes. RESULTS: All allogeneic MSCs were found to be ELA mismatched with the responder leukocytes. MHC II-low and universal blood donor MSCs caused no peripheral blood mononuclear cell (PBMC) proliferation, no increase in B cells, and no activation of CD8 lymphocytes. Universal blood donor MSCs stimulated a significant increase in the number of T regulatory cells. Neutrophil interaction with MSCs showed that universal blood donor and MHC II-high allogeneic MSCs at the 6 h time point in co-culture caused greater neutrophil activation than the other co-culture groups. Complement-mediated cytotoxicity did not consistently cause MSC death in cultures with active complement as compared to those with inactivated complement. Gene expression assays revealed that the universal blood donor group and the MHC II-low MSCs were more metabolically active both in the anabolic and catabolic gene categories when cultured with allogeneic lymphocytes as compared to the other co-cultures. These upregulated genes included CD59, FGF-2, HGF, IDO, IL-10, IL-RA, IL-2, SOX2, TGF-β1, ADAMSTS-4, ADAMSTS-5, CCL2, CXCLB/IL-8, IFNγ, IL-1β, and TNFα. CONCLUSIONS: MHC II-low MSCs are the most appropriate type of allogeneic MSC to prevent activation of the innate and cell-mediated component of the adaptive immune systems and have increased gene expression as compared to other allogeneic MSCs.
dc.description.confidentialfalse
dc.edition.editionDecember 2021
dc.format.pagination570-
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/34772445
dc.identifier.citationKamm JL, Riley CB, Parlane NA, Gee EK, McIlwraith CW. (2021). Immune response to allogeneic equine mesenchymal stromal cells.. Stem Cell Res Ther. 12. 1. (pp. 570-).
dc.identifier.doi10.1186/s13287-021-02624-y
dc.identifier.eissn1757-6512
dc.identifier.elements-typejournal-article
dc.identifier.issn1757-6512
dc.identifier.numberARTN 570
dc.identifier.pii10.1186/s13287-021-02624-y
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/70970
dc.languageeng
dc.publisherBioMed Central Ltd
dc.publisher.urihttps://stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02624-y
dc.relation.isPartOfStem Cell Res Ther
dc.rights(c) 2021 The Author/s
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAllogeneic
dc.subjectEquine
dc.subjectImmune
dc.subjectLymphocyte
dc.subjectAnimals
dc.subjectBone Marrow Cells
dc.subjectCells, Cultured
dc.subjectHematopoietic Stem Cell Transplantation
dc.subjectHorses
dc.subjectImmunity
dc.subjectLeukocytes, Mononuclear
dc.subjectMesenchymal Stem Cells
dc.titleImmune response to allogeneic equine mesenchymal stromal cells
dc.typeJournal article
pubs.elements-id449577
pubs.organisational-groupOther
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