Anticoagulants interfere with the angiogenic and regenerative responses mediated by platelets

Autores
Oneto, Paula; Zubiry, Paula Romina; Schattner, Mirta Ana; Etulain, Julia
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background and aims: Platelet rich plasma (PRP) obtained from blood anticoagulated with acid-citrate-dextrose (ACD) or sodium-citrate (SC) is used for regenerative medicine as source of platelet-derived growth factors. Allergic reactions against citrate were reported in patients after local injection of PRP allowing us to hypothesize that anticoagulants exert a harmful and local effect that interferes with the regenerative proprieties of platelets. Herein we test this hypothesis by analyzing the effect of ACD and SC on angiogenic and regenerative responses mediated by platelets.Methods: PRP was obtained from SC- or ACD-anticoagulated blood; platelets were lysed to release growth factors; and PRP releasates (PRPr) were used to induce in vitro endothelial proliferation and 2D-migration, and regeneration of mouse skin wounds.Results: We first compared proliferation and migration of endothelial cells mediated by anticoagulated-PRPr supplemented or not with CaCl2. Alteration of endothelial adhesion and impediment of proliferation and migration was observed without CaCl2. Although endothelial morphology was normalized in SC- and ACD-PRPr after calcium restitution, angiogenic responses were only markedly induced by SC-PRPr. In vivo studies revealed a delay in mouse skin regeneration after treatment with anticoagulated-PRPr without CaCl2. Healing was only induced after calcium restitution in SC- but ACD-PRPr. Moreover, the development of inflammatory intradermal papules was evidenced after injection of ACD-PRPr. Supplementation of SC-PRPr with the equivalent concentration of dextrose (D-Glucose, 18 mM) present in ACD-PRPr resulted in reduction of endothelial proliferation and migration, delay of mouse skin regeneration and development of intradermal papules. Finally, collecting blood with half amount of SC significantly improved all the angiogenic and regenerative responses mediated by PRPr. In contrast, the delay of skin regeneration and the development of inflammatory papules remained stable after dilution of ACD.Conclusion: Our findings indicate that (1) calcium restitution is required to impair the cellular and tissue alterations induced by citrated-anticoagulants contained in PRP; (2) ACD-derived dextrose confers anti-angiogenic, anti-regenerative and pro-inflammatory proprieties to PRP; and (3) half concentration of SC improves the angiogenesis and regeneration mediated by PRP.
Fil: Oneto, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Zubiry, Paula Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
ANTICOAGULANT
PLATELETS
REGENERATIVE MEDICINE
PLATELET-RICH-PLASMA
TRISODIUM-CITRATE
ANGIOGENESIS
ACID-CITRATE-DEXTROSE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/146512
Acceder
id CONICETDig_ba9a37e994e182ef0bd97a1bad922075
oai_identifier_str oai:ri.conicet.gov.ar:11336/146512
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Anticoagulants interfere with the angiogenic and regenerative responses mediated by plateletsOneto, PaulaZubiry, Paula RominaSchattner, Mirta AnaEtulain, JuliaANTICOAGULANTPLATELETSREGENERATIVE MEDICINEPLATELET-RICH-PLASMATRISODIUM-CITRATEANGIOGENESISACID-CITRATE-DEXTROSEhttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3Background and aims: Platelet rich plasma (PRP) obtained from blood anticoagulated with acid-citrate-dextrose (ACD) or sodium-citrate (SC) is used for regenerative medicine as source of platelet-derived growth factors. Allergic reactions against citrate were reported in patients after local injection of PRP allowing us to hypothesize that anticoagulants exert a harmful and local effect that interferes with the regenerative proprieties of platelets. Herein we test this hypothesis by analyzing the effect of ACD and SC on angiogenic and regenerative responses mediated by platelets.Methods: PRP was obtained from SC- or ACD-anticoagulated blood; platelets were lysed to release growth factors; and PRP releasates (PRPr) were used to induce in vitro endothelial proliferation and 2D-migration, and regeneration of mouse skin wounds.Results: We first compared proliferation and migration of endothelial cells mediated by anticoagulated-PRPr supplemented or not with CaCl2. Alteration of endothelial adhesion and impediment of proliferation and migration was observed without CaCl2. Although endothelial morphology was normalized in SC- and ACD-PRPr after calcium restitution, angiogenic responses were only markedly induced by SC-PRPr. In vivo studies revealed a delay in mouse skin regeneration after treatment with anticoagulated-PRPr without CaCl2. Healing was only induced after calcium restitution in SC- but ACD-PRPr. Moreover, the development of inflammatory intradermal papules was evidenced after injection of ACD-PRPr. Supplementation of SC-PRPr with the equivalent concentration of dextrose (D-Glucose, 18 mM) present in ACD-PRPr resulted in reduction of endothelial proliferation and migration, delay of mouse skin regeneration and development of intradermal papules. Finally, collecting blood with half amount of SC significantly improved all the angiogenic and regenerative responses mediated by PRPr. In contrast, the delay of skin regeneration and the development of inflammatory papules remained stable after dilution of ACD.Conclusion: Our findings indicate that (1) calcium restitution is required to impair the cellular and tissue alterations induced by citrated-anticoagulants contained in PRP; (2) ACD-derived dextrose confers anti-angiogenic, anti-regenerative and pro-inflammatory proprieties to PRP; and (3) half concentration of SC improves the angiogenesis and regeneration mediated by PRP.Fil: Oneto, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Zubiry, Paula Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFrontiers Media2020-03-20info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/146512Oneto, Paula; Zubiry, Paula Romina; Schattner, Mirta Ana; Etulain, Julia; Anticoagulants interfere with the angiogenic and regenerative responses mediated by platelets; Frontiers Media; Frontiers in Bioengineering and Biotechnology; 8; 223; 20-3-2020; 1-122296-4185CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fbioe.2020.00223info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fbioe.2020.00223/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:37:02Zoai:ri.conicet.gov.ar:11336/146512instacron: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:34982025-10-15 15:37:03.17CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Anticoagulants interfere with the angiogenic and regenerative responses mediated by platelets
title Anticoagulants interfere with the angiogenic and regenerative responses mediated by platelets
spellingShingle Anticoagulants interfere with the angiogenic and regenerative responses mediated by platelets
Oneto, Paula
ANTICOAGULANT
PLATELETS
REGENERATIVE MEDICINE
PLATELET-RICH-PLASMA
TRISODIUM-CITRATE
ANGIOGENESIS
ACID-CITRATE-DEXTROSE
title_short Anticoagulants interfere with the angiogenic and regenerative responses mediated by platelets
title_full Anticoagulants interfere with the angiogenic and regenerative responses mediated by platelets
title_fullStr Anticoagulants interfere with the angiogenic and regenerative responses mediated by platelets
title_full_unstemmed Anticoagulants interfere with the angiogenic and regenerative responses mediated by platelets
title_sort Anticoagulants interfere with the angiogenic and regenerative responses mediated by platelets
dc.creator.none.fl_str_mv Oneto, Paula
Zubiry, Paula Romina
Schattner, Mirta Ana
Etulain, Julia
author Oneto, Paula
author_facet Oneto, Paula
Zubiry, Paula Romina
Schattner, Mirta Ana
Etulain, Julia
author_role author
author2 Zubiry, Paula Romina
Schattner, Mirta Ana
Etulain, Julia
author2_role author
author
author
dc.subject.none.fl_str_mv ANTICOAGULANT
PLATELETS
REGENERATIVE MEDICINE
PLATELET-RICH-PLASMA
TRISODIUM-CITRATE
ANGIOGENESIS
ACID-CITRATE-DEXTROSE
topic ANTICOAGULANT
PLATELETS
REGENERATIVE MEDICINE
PLATELET-RICH-PLASMA
TRISODIUM-CITRATE
ANGIOGENESIS
ACID-CITRATE-DEXTROSE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background and aims: Platelet rich plasma (PRP) obtained from blood anticoagulated with acid-citrate-dextrose (ACD) or sodium-citrate (SC) is used for regenerative medicine as source of platelet-derived growth factors. Allergic reactions against citrate were reported in patients after local injection of PRP allowing us to hypothesize that anticoagulants exert a harmful and local effect that interferes with the regenerative proprieties of platelets. Herein we test this hypothesis by analyzing the effect of ACD and SC on angiogenic and regenerative responses mediated by platelets.Methods: PRP was obtained from SC- or ACD-anticoagulated blood; platelets were lysed to release growth factors; and PRP releasates (PRPr) were used to induce in vitro endothelial proliferation and 2D-migration, and regeneration of mouse skin wounds.Results: We first compared proliferation and migration of endothelial cells mediated by anticoagulated-PRPr supplemented or not with CaCl2. Alteration of endothelial adhesion and impediment of proliferation and migration was observed without CaCl2. Although endothelial morphology was normalized in SC- and ACD-PRPr after calcium restitution, angiogenic responses were only markedly induced by SC-PRPr. In vivo studies revealed a delay in mouse skin regeneration after treatment with anticoagulated-PRPr without CaCl2. Healing was only induced after calcium restitution in SC- but ACD-PRPr. Moreover, the development of inflammatory intradermal papules was evidenced after injection of ACD-PRPr. Supplementation of SC-PRPr with the equivalent concentration of dextrose (D-Glucose, 18 mM) present in ACD-PRPr resulted in reduction of endothelial proliferation and migration, delay of mouse skin regeneration and development of intradermal papules. Finally, collecting blood with half amount of SC significantly improved all the angiogenic and regenerative responses mediated by PRPr. In contrast, the delay of skin regeneration and the development of inflammatory papules remained stable after dilution of ACD.Conclusion: Our findings indicate that (1) calcium restitution is required to impair the cellular and tissue alterations induced by citrated-anticoagulants contained in PRP; (2) ACD-derived dextrose confers anti-angiogenic, anti-regenerative and pro-inflammatory proprieties to PRP; and (3) half concentration of SC improves the angiogenesis and regeneration mediated by PRP.
Fil: Oneto, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Zubiry, Paula Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Background and aims: Platelet rich plasma (PRP) obtained from blood anticoagulated with acid-citrate-dextrose (ACD) or sodium-citrate (SC) is used for regenerative medicine as source of platelet-derived growth factors. Allergic reactions against citrate were reported in patients after local injection of PRP allowing us to hypothesize that anticoagulants exert a harmful and local effect that interferes with the regenerative proprieties of platelets. Herein we test this hypothesis by analyzing the effect of ACD and SC on angiogenic and regenerative responses mediated by platelets.Methods: PRP was obtained from SC- or ACD-anticoagulated blood; platelets were lysed to release growth factors; and PRP releasates (PRPr) were used to induce in vitro endothelial proliferation and 2D-migration, and regeneration of mouse skin wounds.Results: We first compared proliferation and migration of endothelial cells mediated by anticoagulated-PRPr supplemented or not with CaCl2. Alteration of endothelial adhesion and impediment of proliferation and migration was observed without CaCl2. Although endothelial morphology was normalized in SC- and ACD-PRPr after calcium restitution, angiogenic responses were only markedly induced by SC-PRPr. In vivo studies revealed a delay in mouse skin regeneration after treatment with anticoagulated-PRPr without CaCl2. Healing was only induced after calcium restitution in SC- but ACD-PRPr. Moreover, the development of inflammatory intradermal papules was evidenced after injection of ACD-PRPr. Supplementation of SC-PRPr with the equivalent concentration of dextrose (D-Glucose, 18 mM) present in ACD-PRPr resulted in reduction of endothelial proliferation and migration, delay of mouse skin regeneration and development of intradermal papules. Finally, collecting blood with half amount of SC significantly improved all the angiogenic and regenerative responses mediated by PRPr. In contrast, the delay of skin regeneration and the development of inflammatory papules remained stable after dilution of ACD.Conclusion: Our findings indicate that (1) calcium restitution is required to impair the cellular and tissue alterations induced by citrated-anticoagulants contained in PRP; (2) ACD-derived dextrose confers anti-angiogenic, anti-regenerative and pro-inflammatory proprieties to PRP; and (3) half concentration of SC improves the angiogenesis and regeneration mediated by PRP.
publishDate 2020
dc.date.none.fl_str_mv 2020-03-20
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/146512
Oneto, Paula; Zubiry, Paula Romina; Schattner, Mirta Ana; Etulain, Julia; Anticoagulants interfere with the angiogenic and regenerative responses mediated by platelets; Frontiers Media; Frontiers in Bioengineering and Biotechnology; 8; 223; 20-3-2020; 1-12
2296-4185
CONICET Digital
CONICET
url http://hdl.handle.net/11336/146512
identifier_str_mv Oneto, Paula; Zubiry, Paula Romina; Schattner, Mirta Ana; Etulain, Julia; Anticoagulants interfere with the angiogenic and regenerative responses mediated by platelets; Frontiers Media; Frontiers in Bioengineering and Biotechnology; 8; 223; 20-3-2020; 1-12
2296-4185
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fbioe.2020.00223
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fbioe.2020.00223/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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
_version_ 1846083492352360448
score 13.22299

Publicaciones similares