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In Vitro Conditioning of Adipose-Derived Mesenchymal Stem Cells by the Endothelial Microenvironment: Modeling Cell Responsiveness towards Non-Genetic Correction of Haemophilia A

In recent decades, the use of adult multipotent stem cells has paved the way for the identification of new therapeutic approaches for the treatment of monogenic diseases such as Haemophilia A. Being already studied for regenerative purposes, adipose-derived mesenchymal stem cells (Ad-MSCs) are still...

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Autores principales: Barbon, Silvia, Stocco, Elena, Rajendran, Senthilkumar, Zardo, Lorena, Macchi, Veronica, Grandi, Claudio, Tagariello, Giuseppe, Porzionato, Andrea, Radossi, Paolo, De Caro, Raffaele, Parnigotto, Pier Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266329/
https://www.ncbi.nlm.nih.gov/pubmed/35806285
http://dx.doi.org/10.3390/ijms23137282
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author Barbon, Silvia
Stocco, Elena
Rajendran, Senthilkumar
Zardo, Lorena
Macchi, Veronica
Grandi, Claudio
Tagariello, Giuseppe
Porzionato, Andrea
Radossi, Paolo
De Caro, Raffaele
Parnigotto, Pier Paolo
author_facet Barbon, Silvia
Stocco, Elena
Rajendran, Senthilkumar
Zardo, Lorena
Macchi, Veronica
Grandi, Claudio
Tagariello, Giuseppe
Porzionato, Andrea
Radossi, Paolo
De Caro, Raffaele
Parnigotto, Pier Paolo
author_sort Barbon, Silvia
collection PubMed
description In recent decades, the use of adult multipotent stem cells has paved the way for the identification of new therapeutic approaches for the treatment of monogenic diseases such as Haemophilia A. Being already studied for regenerative purposes, adipose-derived mesenchymal stem cells (Ad-MSCs) are still poorly considered for Haemophilia A cell therapy and their capacity to produce coagulation factor VIII (FVIII) after proper stimulation and without resorting to gene transfection. In this work, Ad-MSCs were in vitro conditioned towards the endothelial lineage, considered to be responsible for coagulation factor production. The cells were cultured in an inductive medium enriched with endothelial growth factors for up to 21 days. In addition to significantly responding to the chemotactic endothelial stimuli, the cell populations started to form capillary-like structures and up-regulated the expression of specific endothelial markers (CD34, PDGFRα, VEGFR2, VE-cadherin, CD31, and vWF). A dot blot protein study detected the presence of FVIII in culture media collected from both unstimulated and stimulated Ad-MSCs. Remarkably, the activated partial thromboplastin time test demonstrated that the clot formation was accelerated, and FVIII activity was enhanced when FVIII deficient plasma was mixed with culture media from the untreated/stimulated Ad-MSCs. Overall, the collected evidence supported a possible Ad-MSC contribution to HA correction via specific stimulation by the endothelial microenvironment and without any need for gene transfection.
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spelling pubmed-92663292022-07-09 In Vitro Conditioning of Adipose-Derived Mesenchymal Stem Cells by the Endothelial Microenvironment: Modeling Cell Responsiveness towards Non-Genetic Correction of Haemophilia A Barbon, Silvia Stocco, Elena Rajendran, Senthilkumar Zardo, Lorena Macchi, Veronica Grandi, Claudio Tagariello, Giuseppe Porzionato, Andrea Radossi, Paolo De Caro, Raffaele Parnigotto, Pier Paolo Int J Mol Sci Article In recent decades, the use of adult multipotent stem cells has paved the way for the identification of new therapeutic approaches for the treatment of monogenic diseases such as Haemophilia A. Being already studied for regenerative purposes, adipose-derived mesenchymal stem cells (Ad-MSCs) are still poorly considered for Haemophilia A cell therapy and their capacity to produce coagulation factor VIII (FVIII) after proper stimulation and without resorting to gene transfection. In this work, Ad-MSCs were in vitro conditioned towards the endothelial lineage, considered to be responsible for coagulation factor production. The cells were cultured in an inductive medium enriched with endothelial growth factors for up to 21 days. In addition to significantly responding to the chemotactic endothelial stimuli, the cell populations started to form capillary-like structures and up-regulated the expression of specific endothelial markers (CD34, PDGFRα, VEGFR2, VE-cadherin, CD31, and vWF). A dot blot protein study detected the presence of FVIII in culture media collected from both unstimulated and stimulated Ad-MSCs. Remarkably, the activated partial thromboplastin time test demonstrated that the clot formation was accelerated, and FVIII activity was enhanced when FVIII deficient plasma was mixed with culture media from the untreated/stimulated Ad-MSCs. Overall, the collected evidence supported a possible Ad-MSC contribution to HA correction via specific stimulation by the endothelial microenvironment and without any need for gene transfection. MDPI 2022-06-30 /pmc/articles/PMC9266329/ /pubmed/35806285 http://dx.doi.org/10.3390/ijms23137282 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Barbon, Silvia
Stocco, Elena
Rajendran, Senthilkumar
Zardo, Lorena
Macchi, Veronica
Grandi, Claudio
Tagariello, Giuseppe
Porzionato, Andrea
Radossi, Paolo
De Caro, Raffaele
Parnigotto, Pier Paolo
In Vitro Conditioning of Adipose-Derived Mesenchymal Stem Cells by the Endothelial Microenvironment: Modeling Cell Responsiveness towards Non-Genetic Correction of Haemophilia A
title In Vitro Conditioning of Adipose-Derived Mesenchymal Stem Cells by the Endothelial Microenvironment: Modeling Cell Responsiveness towards Non-Genetic Correction of Haemophilia A
title_full In Vitro Conditioning of Adipose-Derived Mesenchymal Stem Cells by the Endothelial Microenvironment: Modeling Cell Responsiveness towards Non-Genetic Correction of Haemophilia A
title_fullStr In Vitro Conditioning of Adipose-Derived Mesenchymal Stem Cells by the Endothelial Microenvironment: Modeling Cell Responsiveness towards Non-Genetic Correction of Haemophilia A
title_full_unstemmed In Vitro Conditioning of Adipose-Derived Mesenchymal Stem Cells by the Endothelial Microenvironment: Modeling Cell Responsiveness towards Non-Genetic Correction of Haemophilia A
title_short In Vitro Conditioning of Adipose-Derived Mesenchymal Stem Cells by the Endothelial Microenvironment: Modeling Cell Responsiveness towards Non-Genetic Correction of Haemophilia A
title_sort in vitro conditioning of adipose-derived mesenchymal stem cells by the endothelial microenvironment: modeling cell responsiveness towards non-genetic correction of haemophilia a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266329/
https://www.ncbi.nlm.nih.gov/pubmed/35806285
http://dx.doi.org/10.3390/ijms23137282
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