Local Adoptive Transfer of Plasmacytoid Dendritic Cells as a Novel Therapeutic Approach for Corneal Neovascularization

Autores
Arsia, Jamali; Lopez, Maria J.; Harris, Deshea L; Sendra, Victor German; Pondelis, Nicholas; Ortiz, Gustavo; Hamrah, Pedram
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Purpose : We have recently shown that plasmacytoid dendritic cells (pDCs) exert angiostatic properties. The aim of this study is to evaluate the therapeutic efficacy of local adoptive transfer of pDCs in treating corneal neovascularization (NV). Methods : Corneas of 6-8 week-old male wildtype (WT) C57BL/6 mice underwent suture placement to induce corneal NV. Splenic GFP+ pDCs from DPE-GFP×RAG1-/- mice and WT CD11b+ myeloid cells were isolated. After trephination, 104 pDCs, CD11b+ cells, or PBS control were locally applied onto the corneas using Tisseel fibrin sealant. On day 7, corneas were stained for CD31 (vascular marker) and underwent confocal microscopy. Length of NV and the density of adoptively-transferred GFP+ pDCs were measured by ImageJ. Relative mRNA level of anti-angiogenic molecule endostatin was quantified in the corneas using qRT-PCR. ANOVA with LSD post-hoc test was used to assess statistical significance. p<0.05 was considered significant. Results : Confocal microscopy confirmed successful transfer of GFP+ pDCs to both central (452.8±39.1 cells/mm2) and peripheral corneas (435.1±52.6) on day 2 following local application of pDCs. qRT-PCR showed that local adoptive transfer of pDCs was accompanied by 4.7-fold increase in the mRNA level of anti-angiogenic molecule endostatin compared with fibrin sealant-only control (p=0.009) and 2.3-fold increase compared with adoptive transfer of CD11b+ cells (p=0.03). One-time adoptive transfer of pDCs significantly reduced NV length on day 7 following suture placement (350.1±43.4 µm), compared with transfer of CD11b+ cells (477.0±33.9 µm; p=0.004) as well as fibrin sealant-only controls (454.1±36.5 µm; p=0.01). Conclusions : Local adoptive transfer of pDCs can limit corneal NV following suture placement and may serve as a novel cell-based therapeutic approach to treat corneal NV.
Fil: Arsia, Jamali. Tufts Medical Center; Estados Unidos
Fil: Lopez, Maria J.. Tufts Medical Center; Estados Unidos
Fil: Harris, Deshea L. Tufts Medical Center; Estados Unidos
Fil: Sendra, Victor German. Tufts Medical Center; Estados Unidos. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pondelis, Nicholas. Tufts Medical Center; Estados Unidos
Fil: Ortiz, Gustavo. Tufts Medical Center; Estados Unidos
Fil: Hamrah, Pedram. Tufts Medical Center; Estados Unidos. New England Eye Center; Estados Unidos
ARVO annual meeting 2019
Vancouver
Canadá
Association for Research in Vision and Ophthalmology
Materia
Plasmacytoid Dendritic Cells
Adoptive transfer
Cornea
Neovascularization
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/162025
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/162025
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Local Adoptive Transfer of Plasmacytoid Dendritic Cells as a Novel Therapeutic Approach for Corneal NeovascularizationArsia, JamaliLopez, Maria J.Harris, Deshea LSendra, Victor GermanPondelis, NicholasOrtiz, GustavoHamrah, PedramPlasmacytoid Dendritic CellsAdoptive transferCorneaNeovascularizationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Purpose : We have recently shown that plasmacytoid dendritic cells (pDCs) exert angiostatic properties. The aim of this study is to evaluate the therapeutic efficacy of local adoptive transfer of pDCs in treating corneal neovascularization (NV). Methods : Corneas of 6-8 week-old male wildtype (WT) C57BL/6 mice underwent suture placement to induce corneal NV. Splenic GFP+ pDCs from DPE-GFP×RAG1-/- mice and WT CD11b+ myeloid cells were isolated. After trephination, 104 pDCs, CD11b+ cells, or PBS control were locally applied onto the corneas using Tisseel fibrin sealant. On day 7, corneas were stained for CD31 (vascular marker) and underwent confocal microscopy. Length of NV and the density of adoptively-transferred GFP+ pDCs were measured by ImageJ. Relative mRNA level of anti-angiogenic molecule endostatin was quantified in the corneas using qRT-PCR. ANOVA with LSD post-hoc test was used to assess statistical significance. p<0.05 was considered significant. Results : Confocal microscopy confirmed successful transfer of GFP+ pDCs to both central (452.8±39.1 cells/mm2) and peripheral corneas (435.1±52.6) on day 2 following local application of pDCs. qRT-PCR showed that local adoptive transfer of pDCs was accompanied by 4.7-fold increase in the mRNA level of anti-angiogenic molecule endostatin compared with fibrin sealant-only control (p=0.009) and 2.3-fold increase compared with adoptive transfer of CD11b+ cells (p=0.03). One-time adoptive transfer of pDCs significantly reduced NV length on day 7 following suture placement (350.1±43.4 µm), compared with transfer of CD11b+ cells (477.0±33.9 µm; p=0.004) as well as fibrin sealant-only controls (454.1±36.5 µm; p=0.01). Conclusions : Local adoptive transfer of pDCs can limit corneal NV following suture placement and may serve as a novel cell-based therapeutic approach to treat corneal NV.Fil: Arsia, Jamali. Tufts Medical Center; Estados UnidosFil: Lopez, Maria J.. Tufts Medical Center; Estados UnidosFil: Harris, Deshea L. Tufts Medical Center; Estados UnidosFil: Sendra, Victor German. Tufts Medical Center; Estados Unidos. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pondelis, Nicholas. Tufts Medical Center; Estados UnidosFil: Ortiz, Gustavo. Tufts Medical Center; Estados UnidosFil: Hamrah, Pedram. Tufts Medical Center; Estados Unidos. New England Eye Center; Estados UnidosARVO annual meeting 2019VancouverCanadáAssociation for Research in Vision and OphthalmologyAssociation for Research in Vision and Ophthalmology2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectConferenciaJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/162025Local Adoptive Transfer of Plasmacytoid Dendritic Cells as a Novel Therapeutic Approach for Corneal Neovascularization; ARVO annual meeting 2019; Vancouver; Canadá; 2019; 61-610146-04041552-5783CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.arvo.org/annual-meeting/meeting-info/past-annual-meetings/info:eu-repo/semantics/altIdentifier/url/https://iovs.arvojournals.org/article.aspx?articleid=2741482Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:54:04Zoai:ri.conicet.gov.ar:11336/162025instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:54:04.663CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Local Adoptive Transfer of Plasmacytoid Dendritic Cells as a Novel Therapeutic Approach for Corneal Neovascularization
title Local Adoptive Transfer of Plasmacytoid Dendritic Cells as a Novel Therapeutic Approach for Corneal Neovascularization
spellingShingle Local Adoptive Transfer of Plasmacytoid Dendritic Cells as a Novel Therapeutic Approach for Corneal Neovascularization
Arsia, Jamali
Plasmacytoid Dendritic Cells
Adoptive transfer
Cornea
Neovascularization
title_short Local Adoptive Transfer of Plasmacytoid Dendritic Cells as a Novel Therapeutic Approach for Corneal Neovascularization
title_full Local Adoptive Transfer of Plasmacytoid Dendritic Cells as a Novel Therapeutic Approach for Corneal Neovascularization
title_fullStr Local Adoptive Transfer of Plasmacytoid Dendritic Cells as a Novel Therapeutic Approach for Corneal Neovascularization
title_full_unstemmed Local Adoptive Transfer of Plasmacytoid Dendritic Cells as a Novel Therapeutic Approach for Corneal Neovascularization
title_sort Local Adoptive Transfer of Plasmacytoid Dendritic Cells as a Novel Therapeutic Approach for Corneal Neovascularization
dc.creator.none.fl_str_mv Arsia, Jamali
Lopez, Maria J.
Harris, Deshea L
Sendra, Victor German
Pondelis, Nicholas
Ortiz, Gustavo
Hamrah, Pedram
author Arsia, Jamali
author_facet Arsia, Jamali
Lopez, Maria J.
Harris, Deshea L
Sendra, Victor German
Pondelis, Nicholas
Ortiz, Gustavo
Hamrah, Pedram
author_role author
author2 Lopez, Maria J.
Harris, Deshea L
Sendra, Victor German
Pondelis, Nicholas
Ortiz, Gustavo
Hamrah, Pedram
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Plasmacytoid Dendritic Cells
Adoptive transfer
Cornea
Neovascularization
topic Plasmacytoid Dendritic Cells
Adoptive transfer
Cornea
Neovascularization
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Purpose : We have recently shown that plasmacytoid dendritic cells (pDCs) exert angiostatic properties. The aim of this study is to evaluate the therapeutic efficacy of local adoptive transfer of pDCs in treating corneal neovascularization (NV). Methods : Corneas of 6-8 week-old male wildtype (WT) C57BL/6 mice underwent suture placement to induce corneal NV. Splenic GFP+ pDCs from DPE-GFP×RAG1-/- mice and WT CD11b+ myeloid cells were isolated. After trephination, 104 pDCs, CD11b+ cells, or PBS control were locally applied onto the corneas using Tisseel fibrin sealant. On day 7, corneas were stained for CD31 (vascular marker) and underwent confocal microscopy. Length of NV and the density of adoptively-transferred GFP+ pDCs were measured by ImageJ. Relative mRNA level of anti-angiogenic molecule endostatin was quantified in the corneas using qRT-PCR. ANOVA with LSD post-hoc test was used to assess statistical significance. p<0.05 was considered significant. Results : Confocal microscopy confirmed successful transfer of GFP+ pDCs to both central (452.8±39.1 cells/mm2) and peripheral corneas (435.1±52.6) on day 2 following local application of pDCs. qRT-PCR showed that local adoptive transfer of pDCs was accompanied by 4.7-fold increase in the mRNA level of anti-angiogenic molecule endostatin compared with fibrin sealant-only control (p=0.009) and 2.3-fold increase compared with adoptive transfer of CD11b+ cells (p=0.03). One-time adoptive transfer of pDCs significantly reduced NV length on day 7 following suture placement (350.1±43.4 µm), compared with transfer of CD11b+ cells (477.0±33.9 µm; p=0.004) as well as fibrin sealant-only controls (454.1±36.5 µm; p=0.01). Conclusions : Local adoptive transfer of pDCs can limit corneal NV following suture placement and may serve as a novel cell-based therapeutic approach to treat corneal NV.
Fil: Arsia, Jamali. Tufts Medical Center; Estados Unidos
Fil: Lopez, Maria J.. Tufts Medical Center; Estados Unidos
Fil: Harris, Deshea L. Tufts Medical Center; Estados Unidos
Fil: Sendra, Victor German. Tufts Medical Center; Estados Unidos. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pondelis, Nicholas. Tufts Medical Center; Estados Unidos
Fil: Ortiz, Gustavo. Tufts Medical Center; Estados Unidos
Fil: Hamrah, Pedram. Tufts Medical Center; Estados Unidos. New England Eye Center; Estados Unidos
ARVO annual meeting 2019
Vancouver
Canadá
Association for Research in Vision and Ophthalmology
description Purpose : We have recently shown that plasmacytoid dendritic cells (pDCs) exert angiostatic properties. The aim of this study is to evaluate the therapeutic efficacy of local adoptive transfer of pDCs in treating corneal neovascularization (NV). Methods : Corneas of 6-8 week-old male wildtype (WT) C57BL/6 mice underwent suture placement to induce corneal NV. Splenic GFP+ pDCs from DPE-GFP×RAG1-/- mice and WT CD11b+ myeloid cells were isolated. After trephination, 104 pDCs, CD11b+ cells, or PBS control were locally applied onto the corneas using Tisseel fibrin sealant. On day 7, corneas were stained for CD31 (vascular marker) and underwent confocal microscopy. Length of NV and the density of adoptively-transferred GFP+ pDCs were measured by ImageJ. Relative mRNA level of anti-angiogenic molecule endostatin was quantified in the corneas using qRT-PCR. ANOVA with LSD post-hoc test was used to assess statistical significance. p<0.05 was considered significant. Results : Confocal microscopy confirmed successful transfer of GFP+ pDCs to both central (452.8±39.1 cells/mm2) and peripheral corneas (435.1±52.6) on day 2 following local application of pDCs. qRT-PCR showed that local adoptive transfer of pDCs was accompanied by 4.7-fold increase in the mRNA level of anti-angiogenic molecule endostatin compared with fibrin sealant-only control (p=0.009) and 2.3-fold increase compared with adoptive transfer of CD11b+ cells (p=0.03). One-time adoptive transfer of pDCs significantly reduced NV length on day 7 following suture placement (350.1±43.4 µm), compared with transfer of CD11b+ cells (477.0±33.9 µm; p=0.004) as well as fibrin sealant-only controls (454.1±36.5 µm; p=0.01). Conclusions : Local adoptive transfer of pDCs can limit corneal NV following suture placement and may serve as a novel cell-based therapeutic approach to treat corneal NV.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Conferencia
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/162025
Local Adoptive Transfer of Plasmacytoid Dendritic Cells as a Novel Therapeutic Approach for Corneal Neovascularization; ARVO annual meeting 2019; Vancouver; Canadá; 2019; 61-61
0146-0404
1552-5783
CONICET Digital
CONICET
url http://hdl.handle.net/11336/162025
identifier_str_mv Local Adoptive Transfer of Plasmacytoid Dendritic Cells as a Novel Therapeutic Approach for Corneal Neovascularization; ARVO annual meeting 2019; Vancouver; Canadá; 2019; 61-61
0146-0404
1552-5783
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.arvo.org/annual-meeting/meeting-info/past-annual-meetings/
info:eu-repo/semantics/altIdentifier/url/https://iovs.arvojournals.org/article.aspx?articleid=2741482
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Association for Research in Vision and Ophthalmology
publisher.none.fl_str_mv Association for Research in Vision and Ophthalmology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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