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

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 d...

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Autores principales: Palma, María Belén, Luzzani, Carlos, Andrini, Laura B., Riccillo, Fernando, Buero, Guillermo, Pelinski, Pablo, Inda, Ana M, Errecalde, Ana Lía, Miriuka, Santiago, Carosella, Edgardo D., Garcia, Marcela N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120529/
https://www.ncbi.nlm.nih.gov/pubmed/33975446
http://dx.doi.org/10.1177/0963689721993774
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author Palma, María Belén
Luzzani, Carlos
Andrini, Laura B.
Riccillo, Fernando
Buero, Guillermo
Pelinski, Pablo
Inda, Ana M
Errecalde, Ana Lía
Miriuka, Santiago
Carosella, Edgardo D.
Garcia, Marcela N.
author_facet Palma, María Belén
Luzzani, Carlos
Andrini, Laura B.
Riccillo, Fernando
Buero, Guillermo
Pelinski, Pablo
Inda, Ana M
Errecalde, Ana Lía
Miriuka, Santiago
Carosella, Edgardo D.
Garcia, Marcela N.
author_sort Palma, María Belén
collection PubMed
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.
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spelling pubmed-81205292021-05-21 Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem Cells Palma, María Belén Luzzani, Carlos Andrini, Laura B. Riccillo, Fernando Buero, Guillermo Pelinski, Pablo Inda, Ana M Errecalde, Ana Lía Miriuka, Santiago Carosella, Edgardo D. Garcia, Marcela N. Cell Transplant Original Article 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. SAGE Publications 2021-05-11 /pmc/articles/PMC8120529/ /pubmed/33975446 http://dx.doi.org/10.1177/0963689721993774 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Article
Palma, María Belén
Luzzani, Carlos
Andrini, Laura B.
Riccillo, Fernando
Buero, Guillermo
Pelinski, Pablo
Inda, Ana M
Errecalde, Ana Lía
Miriuka, Santiago
Carosella, Edgardo D.
Garcia, Marcela N.
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
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_short 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
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120529/
https://www.ncbi.nlm.nih.gov/pubmed/33975446
http://dx.doi.org/10.1177/0963689721993774
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