{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:30:24Z","timestamp":1787614224476,"version":"build-2736575974"},"reference-count":63,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"liberathe relative quantification methol donations from T.E.S. Foundation, Padova, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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, PDGFR\u03b1, 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.<\/jats:p>","DOI":"10.3390\/ijms23137282","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:21:50Z","timestamp":1656634910000},"page":"7282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["In Vitro Conditioning of Adipose-Derived Mesenchymal Stem Cells by the Endothelial Microenvironment: Modeling Cell Responsiveness towards Non-Genetic Correction of Haemophilia A"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2435-0753","authenticated-orcid":false,"given":"Silvia","family":"Barbon","sequence":"first","affiliation":[{"name":"Section of Human Anatomy, Department of Neuroscience, University of Padova, 35121 Padova, Italy"},{"name":"Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling\u2014TES, Onlus, 35030 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Stocco","sequence":"additional","affiliation":[{"name":"Section of Human Anatomy, Department of Neuroscience, University of Padova, 35121 Padova, Italy"},{"name":"Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling\u2014TES, Onlus, 35030 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senthilkumar","family":"Rajendran","sequence":"additional","affiliation":[{"name":"Department of Surgery Oncology and Gastroenterology, University of Padova, 35124 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Zardo","sequence":"additional","affiliation":[{"name":"Haematology and Haemophilia Centre, Castelfranco Veneto Hospital, 31033 Castelfranco Veneto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2335-6897","authenticated-orcid":false,"given":"Veronica","family":"Macchi","sequence":"additional","affiliation":[{"name":"Section of Human Anatomy, Department of Neuroscience, University of Padova, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Grandi","sequence":"additional","affiliation":[{"name":"Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling\u2014TES, Onlus, 35030 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Tagariello","sequence":"additional","affiliation":[{"name":"Haematology and Haemophilia Centre, Castelfranco Veneto Hospital, 31033 Castelfranco Veneto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Porzionato","sequence":"additional","affiliation":[{"name":"Section of Human Anatomy, Department of Neuroscience, University of Padova, 35121 Padova, Italy"},{"name":"Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling\u2014TES, Onlus, 35030 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Radossi","sequence":"additional","affiliation":[{"name":"Haematology and Haemophilia Centre, Castelfranco Veneto Hospital, 31033 Castelfranco Veneto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2307-0277","authenticated-orcid":false,"given":"Raffaele","family":"De Caro","sequence":"additional","affiliation":[{"name":"Section of Human Anatomy, Department of Neuroscience, University of Padova, 35121 Padova, Italy"},{"name":"Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling\u2014TES, Onlus, 35030 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Paolo","family":"Parnigotto","sequence":"additional","affiliation":[{"name":"Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling\u2014TES, Onlus, 35030 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1136\/adc.2005.074278","article-title":"Haemopoietic Stem Cell Transplantation for Genetic Disorders","volume":"90","author":"Steward","year":"2005","journal-title":"Arch. 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