Prevascular Structures Promote Vascularization in Engineered Human Adipose Tissue Constructs upon Implantation

Vascularization is still one of the most important limitations for the survival of engineered tissues after implantation. In this study, we aim to improve the in vivo vascularization of engineered adipose tissue by preforming vascular structures within in vitro-engineered adipose tissue constructs t...

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Main Authors: Femke Verseijden, Sandra J. Posthumus-Van Sluijs, Eric Farrell, Johan W. Van Neck, Steven E. R. Hovius, Stefan O. P. Hofer, Gerjo J. V. M. Van Osch
Format: Article
Language:English
Published: SAGE Publishing 2010-08-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368910X492571
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author Femke Verseijden
Sandra J. Posthumus-Van Sluijs
Eric Farrell
Johan W. Van Neck
Steven E. R. Hovius
Stefan O. P. Hofer
Gerjo J. V. M. Van Osch
author_facet Femke Verseijden
Sandra J. Posthumus-Van Sluijs
Eric Farrell
Johan W. Van Neck
Steven E. R. Hovius
Stefan O. P. Hofer
Gerjo J. V. M. Van Osch
author_sort Femke Verseijden
collection DOAJ
description Vascularization is still one of the most important limitations for the survival of engineered tissues after implantation. In this study, we aim to improve the in vivo vascularization of engineered adipose tissue by preforming vascular structures within in vitro-engineered adipose tissue constructs that can integrate with the host vascular system upon implantation. Different cell culture media were tested and different amounts of human adipose tissue-derived mesenchymal stromal cells (ASC) and human umbilical vein endothelial cells (HUVEC) were combined in spheroid cocultures to obtain optimal conditions for the generation of prevascularized adipose tissue constructs. Immunohistochemistry revealed that prevascular structures were formed in the constructs only when 20% ASC and 80% HUVEC were combined and cultured in a 1:1 mixture of endothelial cell medium and adipogenic medium. Moreover, the ASC in these constructs accumulated lipid and expressed the adipocyte-specific gene fatty acid binding protein-4. Implantation of prevascularized ASC/HUVEC constructs in nude mice resulted in a significantly higher amount of vessels (37 ± 17 vessels/mm 2 ) within the constructs compared to non-prevascularized constructs composed only of ASC (3 ± 4 vessels/mm 2 ). Moreover, a subset of the preformed human vascular structures (3.6 ± 4.2 structures/mm 2 ) anastomosed with the mouse vasculature as indicated by the presence of intravascular red blood cells. Our results indicate that preformed vascular structures within in vitro-engineered adipose tissue constructs can integrate with the host vascular system and improve the vascularization upon implantation.
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spelling doaj.art-b7fdbc4968ae4644b5dbc51419e66e292022-12-22T01:20:30ZengSAGE PublishingCell Transplantation0963-68971555-38922010-08-011910.3727/096368910X492571Prevascular Structures Promote Vascularization in Engineered Human Adipose Tissue Constructs upon ImplantationFemke Verseijden0Sandra J. Posthumus-Van Sluijs1Eric Farrell2Johan W. Van Neck3Steven E. R. Hovius4Stefan O. P. Hofer5Gerjo J. V. M. Van Osch6Department of Plastic and Reconstructive Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsDepartment of Plastic and Reconstructive Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsDepartment of Otorhinolaryngology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsDepartment of Plastic and Reconstructive Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsDepartment of Plastic and Reconstructive Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsDivision of Plastic Surgery, University Health Network, University of Toronto, Toronto, Ontario, CanadaDepartment of Otorhinolaryngology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsVascularization is still one of the most important limitations for the survival of engineered tissues after implantation. In this study, we aim to improve the in vivo vascularization of engineered adipose tissue by preforming vascular structures within in vitro-engineered adipose tissue constructs that can integrate with the host vascular system upon implantation. Different cell culture media were tested and different amounts of human adipose tissue-derived mesenchymal stromal cells (ASC) and human umbilical vein endothelial cells (HUVEC) were combined in spheroid cocultures to obtain optimal conditions for the generation of prevascularized adipose tissue constructs. Immunohistochemistry revealed that prevascular structures were formed in the constructs only when 20% ASC and 80% HUVEC were combined and cultured in a 1:1 mixture of endothelial cell medium and adipogenic medium. Moreover, the ASC in these constructs accumulated lipid and expressed the adipocyte-specific gene fatty acid binding protein-4. Implantation of prevascularized ASC/HUVEC constructs in nude mice resulted in a significantly higher amount of vessels (37 ± 17 vessels/mm 2 ) within the constructs compared to non-prevascularized constructs composed only of ASC (3 ± 4 vessels/mm 2 ). Moreover, a subset of the preformed human vascular structures (3.6 ± 4.2 structures/mm 2 ) anastomosed with the mouse vasculature as indicated by the presence of intravascular red blood cells. Our results indicate that preformed vascular structures within in vitro-engineered adipose tissue constructs can integrate with the host vascular system and improve the vascularization upon implantation.https://doi.org/10.3727/096368910X492571
spellingShingle Femke Verseijden
Sandra J. Posthumus-Van Sluijs
Eric Farrell
Johan W. Van Neck
Steven E. R. Hovius
Stefan O. P. Hofer
Gerjo J. V. M. Van Osch
Prevascular Structures Promote Vascularization in Engineered Human Adipose Tissue Constructs upon Implantation
Cell Transplantation
title Prevascular Structures Promote Vascularization in Engineered Human Adipose Tissue Constructs upon Implantation
title_full Prevascular Structures Promote Vascularization in Engineered Human Adipose Tissue Constructs upon Implantation
title_fullStr Prevascular Structures Promote Vascularization in Engineered Human Adipose Tissue Constructs upon Implantation
title_full_unstemmed Prevascular Structures Promote Vascularization in Engineered Human Adipose Tissue Constructs upon Implantation
title_short Prevascular Structures Promote Vascularization in Engineered Human Adipose Tissue Constructs upon Implantation
title_sort prevascular structures promote vascularization in engineered human adipose tissue constructs upon implantation
url https://doi.org/10.3727/096368910X492571
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AT ericfarrell prevascularstructurespromotevascularizationinengineeredhumanadiposetissueconstructsuponimplantation
AT johanwvanneck prevascularstructurespromotevascularizationinengineeredhumanadiposetissueconstructsuponimplantation
AT stevenerhovius prevascularstructurespromotevascularizationinengineeredhumanadiposetissueconstructsuponimplantation
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