Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem Cells

Autores
Palma, María Belén; Luzzani, Carlos; Andrini, Laura Beatriz; Riccillo, Fernando Luis; Buero, Guillermo; Pelinski, Pablo; Inda, Ana María; Errecalde, Ana Lía; Miriuka, Santiago Gabriel; Carosella, Edgardo; 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-Gþ, CD44þ, CD73þ, CD29þ, CD105þ, CD90þ, 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.
Facultad de Ciencias Médicas
Facultad de Ciencias Naturales y Museo
Materia
Biología
Ciencias Médicas
Wound healing
Allogeneic transplantation
MSC
HLAG
Venous ulcer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/118822

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spelling Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem CellsPalma, María BelénLuzzani, CarlosAndrini, Laura BeatrizRiccillo, Fernando LuisBuero, GuillermoPelinski, PabloInda, Ana MaríaErrecalde, Ana LíaMiriuka, Santiago GabrielCarosella, EdgardoGarcía, Marcela NildaBiologíaCiencias MédicasWound healingAllogeneic transplantationMSCHLAGVenous ulcerIn 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-Gþ, CD44þ, CD73þ, CD29þ, CD105þ, CD90þ, 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.Facultad de Ciencias MédicasFacultad de Ciencias Naturales y Museo2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/118822enginfo:eu-repo/semantics/altIdentifier/issn/0963-6897info:eu-repo/semantics/altIdentifier/issn/1555-3892info:eu-repo/semantics/altIdentifier/doi/10.1177/0963689721993774info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc/4.0/Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:27:59Zoai:sedici.unlp.edu.ar:10915/118822Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:27:59.945SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem Cells
title Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem Cells
spellingShingle Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem Cells
Palma, María Belén
Biología
Ciencias Médicas
Wound healing
Allogeneic transplantation
MSC
HLAG
Venous ulcer
title_short Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem Cells
title_full Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem Cells
title_fullStr Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem Cells
title_full_unstemmed Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem Cells
title_sort Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem Cells
dc.creator.none.fl_str_mv Palma, María Belén
Luzzani, Carlos
Andrini, Laura Beatriz
Riccillo, Fernando Luis
Buero, Guillermo
Pelinski, Pablo
Inda, Ana María
Errecalde, Ana Lía
Miriuka, Santiago Gabriel
Carosella, Edgardo
García, Marcela Nilda
author Palma, María Belén
author_facet Palma, María Belén
Luzzani, Carlos
Andrini, Laura Beatriz
Riccillo, Fernando Luis
Buero, Guillermo
Pelinski, Pablo
Inda, Ana María
Errecalde, Ana Lía
Miriuka, Santiago Gabriel
Carosella, Edgardo
García, Marcela Nilda
author_role author
author2 Luzzani, Carlos
Andrini, Laura Beatriz
Riccillo, Fernando Luis
Buero, Guillermo
Pelinski, Pablo
Inda, Ana María
Errecalde, Ana Lía
Miriuka, Santiago Gabriel
Carosella, Edgardo
García, Marcela Nilda
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Biología
Ciencias Médicas
Wound healing
Allogeneic transplantation
MSC
HLAG
Venous ulcer
topic Biología
Ciencias Médicas
Wound healing
Allogeneic transplantation
MSC
HLAG
Venous ulcer
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-Gþ, CD44þ, CD73þ, CD29þ, CD105þ, CD90þ, 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.
Facultad de Ciencias Médicas
Facultad de Ciencias Naturales y Museo
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-Gþ, CD44þ, CD73þ, CD29þ, CD105þ, CD90þ, 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
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info:eu-repo/semantics/altIdentifier/issn/1555-3892
info:eu-repo/semantics/altIdentifier/doi/10.1177/0963689721993774
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc/4.0/
Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc/4.0/
Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
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