Wound healing treatment by transplantation of umbilical cord mesenchymal stem cell subpopulation

Autores
Palma, Maria Belen; Luzzani, Carlos Daniel; Andrini, Laura Beatríz; Riccillo, Fernando Luis; Buero, Guillermo; Pelinski, Pablo; Inda, Ana María; Errecalde, Ana Lia; Miriuka, Santiago Gabriel; Carosella, Edgardo Delfino; García, Marcela Nilda
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In normal physiological conditions, restoration of a functional epidermal barrier is highly efficient; nevertheless, when it fails, one of the main consequences is a chronic ulcerative skin defect, one of the most frequently recognized complications of diabetes. Most of these chronic venous ulcers do not heal with conventional treatment, leading to the appearance of infections and complications in the patient. Treatments based on the use of autologous mesenchymal stem cells (MSC) have been successful; however, its implementation entails complications. The umbilical cord offers an unlimited source of adult MSC (ucMSC) from the Wharton’s jelly tissue with the same relevant features for clinical applicability and avoiding difficulties. It has recently been characterized by one specific subpopulation derived from ucMSC, the differentiated mesenchymal cells (DMCs). This subpopulation expresses the human leukocyte antigen-G (HLA-G) molecule, a strong immunosuppressive checkpoint, and vascular endothelial growth factor (VEGF), the most potent angiogenic factor. Considering the importance of developing a more effective therapy for wound treatment, especially ulcerative skin lesions, we analyzed DMC safety, efficacy, and therapeutic potential. By immunohistochemistry, umbilical cords HLA-G and VEGF positive were selected. Flow cytometry revealed that 90% of the DMC subpopulation are HLA-G+, CD44+, CD73+, CD29+, CD105+, CD90+, and HLA-DR−. Reverse transcription-polymerase chain reaction revealed the expression of HLA-G in all of DMC subpopulations. Upon co-culture with the DMC, peripheral blood mononuclear cell proliferation was inhibited by 50%. In a xenograft transplantation assay, DMC improved wound healing with no signs of rejection of the transplanted cells in immunocompetent mice. This study confirms that HLA-G allows allogeneic cell transplantation, and VEGF is fundamental for the restoration of the failure in blood supply. DMC population has positive effects on wound healing by promoting local angiogenesis in skin lesions. DMC could play a very important role in regenerative medicine and could be a novel allogeneic cell-therapeutic tool for wound healing.
Fil: Palma, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Luzzani, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Andrini, Laura Beatríz. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina
Fil: Riccillo, Fernando Luis. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
Fil: Buero, Guillermo. Sanatorio Mater Dei; Argentina
Fil: Pelinski, Pablo. Hospital Español; Argentina
Fil: Inda, Ana María. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
Fil: Errecalde, Ana Lia. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
Fil: Miriuka, Santiago Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
Fil: Carosella, Edgardo Delfino. Université Paris Diderot - Paris 7; Francia. Commissariat à L?Énergie Atomique et aux Énergies Alternatives; Francia
Fil: García, Marcela Nilda. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
Materia
ALLOGENEIC TRANSPLANTATION
HLAG
MSC
VENOUS ULCER
WOUND HEALING
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/165234
Acceder
id CONICETDig_4e5807c08224579438cfba9c3fbd96ae
oai_identifier_str oai:ri.conicet.gov.ar:11336/165234
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Wound healing treatment by transplantation of umbilical cord mesenchymal stem cell subpopulationPalma, Maria BelenLuzzani, Carlos DanielAndrini, Laura BeatrízRiccillo, Fernando LuisBuero, GuillermoPelinski, PabloInda, Ana MaríaErrecalde, Ana LiaMiriuka, Santiago GabrielCarosella, Edgardo DelfinoGarcía, Marcela NildaALLOGENEIC TRANSPLANTATIONHLAGMSCVENOUS ULCERWOUND HEALINGhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3In normal physiological conditions, restoration of a functional epidermal barrier is highly efficient; nevertheless, when it fails, one of the main consequences is a chronic ulcerative skin defect, one of the most frequently recognized complications of diabetes. Most of these chronic venous ulcers do not heal with conventional treatment, leading to the appearance of infections and complications in the patient. Treatments based on the use of autologous mesenchymal stem cells (MSC) have been successful; however, its implementation entails complications. The umbilical cord offers an unlimited source of adult MSC (ucMSC) from the Wharton’s jelly tissue with the same relevant features for clinical applicability and avoiding difficulties. It has recently been characterized by one specific subpopulation derived from ucMSC, the differentiated mesenchymal cells (DMCs). This subpopulation expresses the human leukocyte antigen-G (HLA-G) molecule, a strong immunosuppressive checkpoint, and vascular endothelial growth factor (VEGF), the most potent angiogenic factor. Considering the importance of developing a more effective therapy for wound treatment, especially ulcerative skin lesions, we analyzed DMC safety, efficacy, and therapeutic potential. By immunohistochemistry, umbilical cords HLA-G and VEGF positive were selected. Flow cytometry revealed that 90% of the DMC subpopulation are HLA-G+, CD44+, CD73+, CD29+, CD105+, CD90+, and HLA-DR−. Reverse transcription-polymerase chain reaction revealed the expression of HLA-G in all of DMC subpopulations. Upon co-culture with the DMC, peripheral blood mononuclear cell proliferation was inhibited by 50%. In a xenograft transplantation assay, DMC improved wound healing with no signs of rejection of the transplanted cells in immunocompetent mice. This study confirms that HLA-G allows allogeneic cell transplantation, and VEGF is fundamental for the restoration of the failure in blood supply. DMC population has positive effects on wound healing by promoting local angiogenesis in skin lesions. DMC could play a very important role in regenerative medicine and could be a novel allogeneic cell-therapeutic tool for wound healing.Fil: Palma, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Luzzani, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Andrini, Laura Beatríz. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; ArgentinaFil: Riccillo, Fernando Luis. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; ArgentinaFil: Buero, Guillermo. Sanatorio Mater Dei; ArgentinaFil: Pelinski, Pablo. Hospital Español; ArgentinaFil: Inda, Ana María. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; ArgentinaFil: Errecalde, Ana Lia. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; ArgentinaFil: Miriuka, Santiago Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; ArgentinaFil: Carosella, Edgardo Delfino. Université Paris Diderot - Paris 7; Francia. Commissariat à L?Énergie Atomique et aux Énergies Alternatives; FranciaFil: García, Marcela Nilda. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; ArgentinaSAGE Publications2021-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/165234Palma, Maria Belen; Luzzani, Carlos Daniel; Andrini, Laura Beatríz; Riccillo, Fernando Luis; Buero, Guillermo; et al.; Wound healing treatment by transplantation of umbilical cord mesenchymal stem cell subpopulation; SAGE Publications; Cell Transplantation; 30; 5-2021; 1-110963-68971555-3892CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1177/0963689721993774info:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/10.1177/0963689721993774info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-12T09:37:09Zoai:ri.conicet.gov.ar:11336/165234instacron: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:34982025-11-12 09:37:09.709CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Wound healing treatment by transplantation of umbilical cord mesenchymal stem cell subpopulation
title Wound healing treatment by transplantation of umbilical cord mesenchymal stem cell subpopulation
spellingShingle Wound healing treatment by transplantation of umbilical cord mesenchymal stem cell subpopulation
Palma, Maria Belen
ALLOGENEIC TRANSPLANTATION
HLAG
MSC
VENOUS ULCER
WOUND HEALING
title_short Wound healing treatment by transplantation of umbilical cord mesenchymal stem cell subpopulation
title_full Wound healing treatment by transplantation of umbilical cord mesenchymal stem cell subpopulation
title_fullStr Wound healing treatment by transplantation of umbilical cord mesenchymal stem cell subpopulation
title_full_unstemmed Wound healing treatment by transplantation of umbilical cord mesenchymal stem cell subpopulation
title_sort Wound healing treatment by transplantation of umbilical cord mesenchymal stem cell subpopulation
dc.creator.none.fl_str_mv Palma, Maria Belen
Luzzani, Carlos Daniel
Andrini, Laura Beatríz
Riccillo, Fernando Luis
Buero, Guillermo
Pelinski, Pablo
Inda, Ana María
Errecalde, Ana Lia
Miriuka, Santiago Gabriel
Carosella, Edgardo Delfino
García, Marcela Nilda
author Palma, Maria Belen
author_facet Palma, Maria Belen
Luzzani, Carlos Daniel
Andrini, Laura Beatríz
Riccillo, Fernando Luis
Buero, Guillermo
Pelinski, Pablo
Inda, Ana María
Errecalde, Ana Lia
Miriuka, Santiago Gabriel
Carosella, Edgardo Delfino
García, Marcela Nilda
author_role author
author2 Luzzani, Carlos Daniel
Andrini, Laura Beatríz
Riccillo, Fernando Luis
Buero, Guillermo
Pelinski, Pablo
Inda, Ana María
Errecalde, Ana Lia
Miriuka, Santiago Gabriel
Carosella, Edgardo Delfino
García, Marcela Nilda
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ALLOGENEIC TRANSPLANTATION
HLAG
MSC
VENOUS ULCER
WOUND HEALING
topic ALLOGENEIC TRANSPLANTATION
HLAG
MSC
VENOUS ULCER
WOUND HEALING
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In normal physiological conditions, restoration of a functional epidermal barrier is highly efficient; nevertheless, when it fails, one of the main consequences is a chronic ulcerative skin defect, one of the most frequently recognized complications of diabetes. Most of these chronic venous ulcers do not heal with conventional treatment, leading to the appearance of infections and complications in the patient. Treatments based on the use of autologous mesenchymal stem cells (MSC) have been successful; however, its implementation entails complications. The umbilical cord offers an unlimited source of adult MSC (ucMSC) from the Wharton’s jelly tissue with the same relevant features for clinical applicability and avoiding difficulties. It has recently been characterized by one specific subpopulation derived from ucMSC, the differentiated mesenchymal cells (DMCs). This subpopulation expresses the human leukocyte antigen-G (HLA-G) molecule, a strong immunosuppressive checkpoint, and vascular endothelial growth factor (VEGF), the most potent angiogenic factor. Considering the importance of developing a more effective therapy for wound treatment, especially ulcerative skin lesions, we analyzed DMC safety, efficacy, and therapeutic potential. By immunohistochemistry, umbilical cords HLA-G and VEGF positive were selected. Flow cytometry revealed that 90% of the DMC subpopulation are HLA-G+, CD44+, CD73+, CD29+, CD105+, CD90+, and HLA-DR−. Reverse transcription-polymerase chain reaction revealed the expression of HLA-G in all of DMC subpopulations. Upon co-culture with the DMC, peripheral blood mononuclear cell proliferation was inhibited by 50%. In a xenograft transplantation assay, DMC improved wound healing with no signs of rejection of the transplanted cells in immunocompetent mice. This study confirms that HLA-G allows allogeneic cell transplantation, and VEGF is fundamental for the restoration of the failure in blood supply. DMC population has positive effects on wound healing by promoting local angiogenesis in skin lesions. DMC could play a very important role in regenerative medicine and could be a novel allogeneic cell-therapeutic tool for wound healing.
Fil: Palma, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Luzzani, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Andrini, Laura Beatríz. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina
Fil: Riccillo, Fernando Luis. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
Fil: Buero, Guillermo. Sanatorio Mater Dei; Argentina
Fil: Pelinski, Pablo. Hospital Español; Argentina
Fil: Inda, Ana María. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
Fil: Errecalde, Ana Lia. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
Fil: Miriuka, Santiago Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
Fil: Carosella, Edgardo Delfino. Université Paris Diderot - Paris 7; Francia. Commissariat à L?Énergie Atomique et aux Énergies Alternatives; Francia
Fil: García, Marcela Nilda. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
description In normal physiological conditions, restoration of a functional epidermal barrier is highly efficient; nevertheless, when it fails, one of the main consequences is a chronic ulcerative skin defect, one of the most frequently recognized complications of diabetes. Most of these chronic venous ulcers do not heal with conventional treatment, leading to the appearance of infections and complications in the patient. Treatments based on the use of autologous mesenchymal stem cells (MSC) have been successful; however, its implementation entails complications. The umbilical cord offers an unlimited source of adult MSC (ucMSC) from the Wharton’s jelly tissue with the same relevant features for clinical applicability and avoiding difficulties. It has recently been characterized by one specific subpopulation derived from ucMSC, the differentiated mesenchymal cells (DMCs). This subpopulation expresses the human leukocyte antigen-G (HLA-G) molecule, a strong immunosuppressive checkpoint, and vascular endothelial growth factor (VEGF), the most potent angiogenic factor. Considering the importance of developing a more effective therapy for wound treatment, especially ulcerative skin lesions, we analyzed DMC safety, efficacy, and therapeutic potential. By immunohistochemistry, umbilical cords HLA-G and VEGF positive were selected. Flow cytometry revealed that 90% of the DMC subpopulation are HLA-G+, CD44+, CD73+, CD29+, CD105+, CD90+, and HLA-DR−. Reverse transcription-polymerase chain reaction revealed the expression of HLA-G in all of DMC subpopulations. Upon co-culture with the DMC, peripheral blood mononuclear cell proliferation was inhibited by 50%. In a xenograft transplantation assay, DMC improved wound healing with no signs of rejection of the transplanted cells in immunocompetent mice. This study confirms that HLA-G allows allogeneic cell transplantation, and VEGF is fundamental for the restoration of the failure in blood supply. DMC population has positive effects on wound healing by promoting local angiogenesis in skin lesions. DMC could play a very important role in regenerative medicine and could be a novel allogeneic cell-therapeutic tool for wound healing.
publishDate 2021
dc.date.none.fl_str_mv 2021-05
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/11336/165234
Palma, Maria Belen; Luzzani, Carlos Daniel; Andrini, Laura Beatríz; Riccillo, Fernando Luis; Buero, Guillermo; et al.; Wound healing treatment by transplantation of umbilical cord mesenchymal stem cell subpopulation; SAGE Publications; Cell Transplantation; 30; 5-2021; 1-11
0963-6897
1555-3892
CONICET Digital
CONICET
url http://hdl.handle.net/11336/165234
identifier_str_mv Palma, Maria Belen; Luzzani, Carlos Daniel; Andrini, Laura Beatríz; Riccillo, Fernando Luis; Buero, Guillermo; et al.; Wound healing treatment by transplantation of umbilical cord mesenchymal stem cell subpopulation; SAGE Publications; Cell Transplantation; 30; 5-2021; 1-11
0963-6897
1555-3892
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1177/0963689721993774
info:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/10.1177/0963689721993774
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv SAGE Publications
publisher.none.fl_str_mv SAGE Publications
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_ 1848597293799833600
score 12.976206

Publicaciones similares