Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound Repair

Autores
Lombardi, Antonella; Smucler, Joaquin; Palma, Maria Belen; Iribarne, Ailen; la Greca, Alejandro Damián; García, M. N.; Sevlever, Gustavo; Miriuka, Santiago Gabriel; Luzzani, Carlos Daniel
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mesenchymal stem cells (MSCs) have garnered significant attention over the past three decades due to their robust regenerative potential, primarily mediated by their paracrine activity by releasing soluble bioactive factors and extracellular vesicles (EVs). The MSC secretome plays a pivotal role in wound healing by influencing cellular migration, inflammation, angiogenesis, extracellular matrix (ECM) remodeling, and re-epithelialization. SPARC (Secreted Protein Acidic and Rich in Cysteine), a multifunctional ECM glycoprotein involved in tissue repair and remodeling, regulates key processes such as cell migration, proliferation, angiogenesis, and survival. Despite its known role in ECM dynamics, the impact of SPARC expression on the regenerative properties of MSCs remains underexplored.In this study, we hypothesized that SPARC overexpression in MSCs enhances their secretome´s regenerative capacity. Using lentiviral systems, we generated SPARC-overexpressing (+SPARC) and SPARC-knockdown (KD-SPARC) MSCs to investigate SPARC´s role in wound healing. Conditioned media (CM) derived from these MSCs were analyzed in vitro for their effects on human skin keratinocytes and fibroblasts. Our results revealed that SPARC expression significantly influences cell-specific migration and cell cycle. Furthermore, in an in vivo wound healing model, CM from +SPARC MSCs accelerated regeneration, while SPARC absence in MSCs CM delayed the healing process.These findings underscore the critical role of SPARC in modulating MSC secretome composition and enhancing its regenerative efficacy. This study highlights SPARC as a promising therapeutic target for the development of advanced regenerative therapies aimed at improving cutaneous wound healing outcomes.
Fil: Lombardi, Antonella. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: Smucler, Joaquin. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: Palma, Maria Belen. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: Iribarne, Ailen. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: la Greca, Alejandro Damián. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: García, M. N.. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Sevlever, Gustavo. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: Miriuka, Santiago Gabriel. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: Luzzani, Carlos Daniel. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Materia
SPARC
MESENCHYMAL STEM CELLS
SECRETOME
WOUNDF REGENERATION
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:11336/288156
Acceder
id CONICETDig_218b69ec0fe6465606ec33881ac8c256
oai_identifier_str oai:ri.conicet.gov.ar:11336/288156
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound RepairLombardi, AntonellaSmucler, JoaquinPalma, Maria BelenIribarne, Ailenla Greca, Alejandro DamiánGarcía, M. N.Sevlever, GustavoMiriuka, Santiago GabrielLuzzani, Carlos DanielSPARCMESENCHYMAL STEM CELLSSECRETOMEWOUNDF REGENERATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Mesenchymal stem cells (MSCs) have garnered significant attention over the past three decades due to their robust regenerative potential, primarily mediated by their paracrine activity by releasing soluble bioactive factors and extracellular vesicles (EVs). The MSC secretome plays a pivotal role in wound healing by influencing cellular migration, inflammation, angiogenesis, extracellular matrix (ECM) remodeling, and re-epithelialization. SPARC (Secreted Protein Acidic and Rich in Cysteine), a multifunctional ECM glycoprotein involved in tissue repair and remodeling, regulates key processes such as cell migration, proliferation, angiogenesis, and survival. Despite its known role in ECM dynamics, the impact of SPARC expression on the regenerative properties of MSCs remains underexplored.In this study, we hypothesized that SPARC overexpression in MSCs enhances their secretome´s regenerative capacity. Using lentiviral systems, we generated SPARC-overexpressing (+SPARC) and SPARC-knockdown (KD-SPARC) MSCs to investigate SPARC´s role in wound healing. Conditioned media (CM) derived from these MSCs were analyzed in vitro for their effects on human skin keratinocytes and fibroblasts. Our results revealed that SPARC expression significantly influences cell-specific migration and cell cycle. Furthermore, in an in vivo wound healing model, CM from +SPARC MSCs accelerated regeneration, while SPARC absence in MSCs CM delayed the healing process.These findings underscore the critical role of SPARC in modulating MSC secretome composition and enhancing its regenerative efficacy. This study highlights SPARC as a promising therapeutic target for the development of advanced regenerative therapies aimed at improving cutaneous wound healing outcomes.Fil: Lombardi, Antonella. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; ArgentinaFil: Smucler, Joaquin. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; ArgentinaFil: Palma, Maria Belen. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; ArgentinaFil: Iribarne, Ailen. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; ArgentinaFil: la Greca, Alejandro Damián. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; ArgentinaFil: García, M. N.. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Sevlever, Gustavo. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; ArgentinaFil: Miriuka, Santiago Gabriel. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; ArgentinaFil: Luzzani, Carlos Daniel. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; ArgentinaCold Spring Harbor Laboratory Press2026-03-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/288156Lombardi, Antonella; Smucler, Joaquin; Palma, Maria Belen; Iribarne, Ailen; la Greca, Alejandro Damián; et al.; Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound Repair; Cold Spring Harbor Laboratory Press; BioRxiv; 9-3-2026; 1-272692-8205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://doi.org/10.64898/2026.03.07.710278info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.64898/2026.03.07.710278v1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:33:20Zoai:ri.conicet.gov.ar:11336/288156instacron: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:34982026-08-25 14:33:21.281CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound Repair
title Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound Repair
spellingShingle Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound Repair
Lombardi, Antonella
SPARC
MESENCHYMAL STEM CELLS
SECRETOME
WOUNDF REGENERATION
title_short Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound Repair
title_full Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound Repair
title_fullStr Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound Repair
title_full_unstemmed Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound Repair
title_sort Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound Repair
dc.creator.none.fl_str_mv Lombardi, Antonella
Smucler, Joaquin
Palma, Maria Belen
Iribarne, Ailen
la Greca, Alejandro Damián
García, M. N.
Sevlever, Gustavo
Miriuka, Santiago Gabriel
Luzzani, Carlos Daniel
author Lombardi, Antonella
author_facet Lombardi, Antonella
Smucler, Joaquin
Palma, Maria Belen
Iribarne, Ailen
la Greca, Alejandro Damián
García, M. N.
Sevlever, Gustavo
Miriuka, Santiago Gabriel
Luzzani, Carlos Daniel
author_role author
author2 Smucler, Joaquin
Palma, Maria Belen
Iribarne, Ailen
la Greca, Alejandro Damián
García, M. N.
Sevlever, Gustavo
Miriuka, Santiago Gabriel
Luzzani, Carlos Daniel
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv SPARC
MESENCHYMAL STEM CELLS
SECRETOME
WOUNDF REGENERATION
topic SPARC
MESENCHYMAL STEM CELLS
SECRETOME
WOUNDF REGENERATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Mesenchymal stem cells (MSCs) have garnered significant attention over the past three decades due to their robust regenerative potential, primarily mediated by their paracrine activity by releasing soluble bioactive factors and extracellular vesicles (EVs). The MSC secretome plays a pivotal role in wound healing by influencing cellular migration, inflammation, angiogenesis, extracellular matrix (ECM) remodeling, and re-epithelialization. SPARC (Secreted Protein Acidic and Rich in Cysteine), a multifunctional ECM glycoprotein involved in tissue repair and remodeling, regulates key processes such as cell migration, proliferation, angiogenesis, and survival. Despite its known role in ECM dynamics, the impact of SPARC expression on the regenerative properties of MSCs remains underexplored.In this study, we hypothesized that SPARC overexpression in MSCs enhances their secretome´s regenerative capacity. Using lentiviral systems, we generated SPARC-overexpressing (+SPARC) and SPARC-knockdown (KD-SPARC) MSCs to investigate SPARC´s role in wound healing. Conditioned media (CM) derived from these MSCs were analyzed in vitro for their effects on human skin keratinocytes and fibroblasts. Our results revealed that SPARC expression significantly influences cell-specific migration and cell cycle. Furthermore, in an in vivo wound healing model, CM from +SPARC MSCs accelerated regeneration, while SPARC absence in MSCs CM delayed the healing process.These findings underscore the critical role of SPARC in modulating MSC secretome composition and enhancing its regenerative efficacy. This study highlights SPARC as a promising therapeutic target for the development of advanced regenerative therapies aimed at improving cutaneous wound healing outcomes.
Fil: Lombardi, Antonella. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: Smucler, Joaquin. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: Palma, Maria Belen. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: Iribarne, Ailen. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: la Greca, Alejandro Damián. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: García, M. N.. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Sevlever, Gustavo. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: Miriuka, Santiago Gabriel. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
Fil: Luzzani, Carlos Daniel. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina
description Mesenchymal stem cells (MSCs) have garnered significant attention over the past three decades due to their robust regenerative potential, primarily mediated by their paracrine activity by releasing soluble bioactive factors and extracellular vesicles (EVs). The MSC secretome plays a pivotal role in wound healing by influencing cellular migration, inflammation, angiogenesis, extracellular matrix (ECM) remodeling, and re-epithelialization. SPARC (Secreted Protein Acidic and Rich in Cysteine), a multifunctional ECM glycoprotein involved in tissue repair and remodeling, regulates key processes such as cell migration, proliferation, angiogenesis, and survival. Despite its known role in ECM dynamics, the impact of SPARC expression on the regenerative properties of MSCs remains underexplored.In this study, we hypothesized that SPARC overexpression in MSCs enhances their secretome´s regenerative capacity. Using lentiviral systems, we generated SPARC-overexpressing (+SPARC) and SPARC-knockdown (KD-SPARC) MSCs to investigate SPARC´s role in wound healing. Conditioned media (CM) derived from these MSCs were analyzed in vitro for their effects on human skin keratinocytes and fibroblasts. Our results revealed that SPARC expression significantly influences cell-specific migration and cell cycle. Furthermore, in an in vivo wound healing model, CM from +SPARC MSCs accelerated regeneration, while SPARC absence in MSCs CM delayed the healing process.These findings underscore the critical role of SPARC in modulating MSC secretome composition and enhancing its regenerative efficacy. This study highlights SPARC as a promising therapeutic target for the development of advanced regenerative therapies aimed at improving cutaneous wound healing outcomes.
publishDate 2026
dc.date.none.fl_str_mv 2026-03-09
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/11336/288156
Lombardi, Antonella; Smucler, Joaquin; Palma, Maria Belen; Iribarne, Ailen; la Greca, Alejandro Damián; et al.; Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound Repair; Cold Spring Harbor Laboratory Press; BioRxiv; 9-3-2026; 1-27
2692-8205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/288156
identifier_str_mv Lombardi, Antonella; Smucler, Joaquin; Palma, Maria Belen; Iribarne, Ailen; la Greca, Alejandro Damián; et al.; Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound Repair; Cold Spring Harbor Laboratory Press; BioRxiv; 9-3-2026; 1-27
2692-8205
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://doi.org/10.64898/2026.03.07.710278
info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.64898/2026.03.07.710278v1
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.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
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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score 13.265058

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