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dc.contributor.authorAlagesan, Senthilkumar
dc.contributor.authorSanz‐Nogués, Clara
dc.contributor.authorChen, Xizhe
dc.contributor.authorCreane, Michael
dc.contributor.authorRitter, Thomas
dc.contributor.authorCeredig, Rhodri
dc.contributor.authorO'Brien, Timothy
dc.contributor.authorGriffin, Matthew D.
dc.date.accessioned2019-03-11T14:54:20Z
dc.date.available2019-03-11T14:54:20Z
dc.date.issued2018-02-15
dc.identifier.citationAlagesan, Senthilkumar, Sanz-Nogués, Clara, Chen, Xizhe, Creane, Michael, Ritter, Thomas, Ceredig, Rhodri, O'Brien, Timothy, Griffin, Matthew D. (2018). Anti-donor antibody induction following intramuscular injections of allogeneic mesenchymal stromal cells. Immunology & Cell Biology, 96(5), 536-548. doi: doi:10.1111/imcb.12024en_IE
dc.identifier.issn1440-1711
dc.identifier.urihttp://hdl.handle.net/10379/15011
dc.description.abstractAllogeneic mesenchymal stromal cells (allo-MSC) are a promising "off-the-shelf" therapy with anti-inflammatory and pro-repair properties. This study investigated humoral immune responses to intramuscular (IM) injections of allo-MSC. Total and isotype-specific anti-donor IgG and donor-specific complement-mediated lysis were determined in sera from healthy mice 2 weeks after single or repeated IM injections of fully mismatched-MHC allo-MSC with comparison to mice receiving syngeneic MSC, allogeneic splenocytes or saline. In mice subjected to hind limb ischemia (HLI), anti-donor IgG was analyzed following IM allo-MSC injection with and without administration of the T-cell immunosuppressant tacrolimus. Recipients of single and repeated IM allo-MSC developed readily-detectable anti-donor IgG. Serum anti-donor IgG levels were similar to those of allo-splenocyte recipients but had higher IgG1/IgG2a ratio and variable capacity for complement-mediated lysis of donor cells. The induced anti-donor IgG bound readily to allo-MSC and this binding was increased following allo-MSC pretreatment with interferon gamma. In mice with HLI, IM injection of allo-MSC into the ischemic limb was also associated with induction of anti-donor IgG but this was abrogated by tacrolimus (FK-506). The results indicate that allo-MSC are inherently immunogenic when delivered intramuscularly to healthy and ischemic mouse hind limb, but induce an IgG1-skewed humoral response that is suppressed by tacrolimus.en_IE
dc.description.sponsorshipFunding for the project was received from Science Foundation Ireland (REMEDI Strategic Research Cluster [grant number 09/SRC‐B1794, SA, CS‐N, XC, MC, TR, RC, TO'B, MDG]). Additional funding was received from Science Foundation Ireland (CÚRAM Research Centre [grant number 13/RC/2073, TO'B, MDG]); the European Commission (REDDSTAR [EU Framework Programme 7 Consortium Grant Number 305736, TO'B] and NEPHSTROM [EU Horizon2020 Consortium Grant Number 634086, TO'B, MDG]), from the Irish Research Council (grant number EPSPD/2016/38, CS‐N) and from the European Regional Development Fund (all authors). The authors acknowledge the technical assistance of Dr Shirley Hanley and the facilities of the NUI Galway Flow Cytometry Core Facility which are supported by funds from NUI Galway, Science Foundation Ireland, the Irish Government's Programme for Research in Third Level Institutions, Cycle 5 and the European Regional Development Fund.en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherWileyen_IE
dc.relation.ispartofImmunol Cell Biolen
dc.subjectAntibodiesen_IE
dc.subjectcell therapyen_IE
dc.subjectimmunogenicityen_IE
dc.subjectimmunosuppressionen_IE
dc.subjectmesenchymal stromal cellsen_IE
dc.subjectvascular diseaseen_IE
dc.subjectCRITICAL LIMB ISCHEMIAen_IE
dc.subjectSTEM-CELLSen_IE
dc.subjectIN-VIVOen_IE
dc.subjectTHERAPEUTIC PROPERTIESen_IE
dc.subjectBUERGERS-DISEASEen_IE
dc.subjectTRANSPLANTATIONen_IE
dc.subjectMECHANISMSen_IE
dc.subjectDIFFERENTIATIONen_IE
dc.subjectIMMUNOGENICITYen_IE
dc.subjectREJECTIONen_IE
dc.titleAnti-donor antibody induction following intramuscular injections of allogeneic mesenchymal stromal cellsen_IE
dc.typeArticleen_IE
dc.date.updated2019-03-11T12:47:40Z
dc.identifier.doi10.1111/imcb.12024
dc.local.publishedsourcehttps://doi.org/10.1111/imcb.12024en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funderScience Foundation Irelanden_IE
dc.contributor.funderSeventh Framework Programmeen_IE
dc.contributor.funderHorizon 2020en_IE
dc.contributor.funderIrish Research Councilen_IE
dc.contributor.funderEuropean Regional Development Funden_IE
dc.internal.rssid14491368
dc.local.contactMatthew Dallas Griffin, Remedi, Biomedical Sciences Buil, Corrib Village, Dangan, Nui Galway. 5436 Email: matthew.griffin@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionACCEPTED
dcterms.projectinfo:eu-repo/grantAgreement/SFI/SFI Strategic Research Cluster/09/SRC/B1794/IE/SRC REMEDI: REMEDI-2: From Research to Human Therapy/en_IE
dcterms.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/13/RC/2073/IE/C�RAM - Centre for Research in Medical Devices/en_IE
dcterms.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::HEALTH/305736/EU/Repair of Diabetic Damage by Stromal Cell Administration/REDDSTARen_IE
dcterms.projectinfo:eu-repo/grantAgreement/EC/H2020::RIA/634086/EU/Novel Stromal Cell Therapy for Diabetic Kidney Disease/NEPHSTROMen_IE
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