Endothelial Progenitor Cells as a Sole Source for Ex Vivo Seeding of Tissue-Engineered Heart Valves

Purposes: We investigated whether circulating endothelial progenitor cells (EPCs) can be used as a cell source for the creation of a tissue-engineered heart valve (TEHV). Methods: Trileaflet valved conduits were fabricated using nonwoven polyglycolic acid/poly-4-hydroxybutyrate polymer. Ovine periph...

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Main Authors: Sales, Virna L., Mettler, Bret A., Engelmayr, George C., Aikawa, Elena, Bischoff, Joyce, Martin, David P., Exarhopoulos, Alexis, Moses, Marsha A., Schoen, Frederick J., Sacks, Michael S., Mayer, John E.
Other Authors: Harvard University--MIT Division of Health Sciences and Technology
Format: Article
Language:en_US
Published: Mary Ann Liebert, Inc. 2011
Online Access:http://hdl.handle.net/1721.1/62173
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author Sales, Virna L.
Mettler, Bret A.
Engelmayr, George C.
Aikawa, Elena
Bischoff, Joyce
Martin, David P.
Exarhopoulos, Alexis
Moses, Marsha A.
Schoen, Frederick J.
Sacks, Michael S.
Mayer, John E.
author2 Harvard University--MIT Division of Health Sciences and Technology
author_facet Harvard University--MIT Division of Health Sciences and Technology
Sales, Virna L.
Mettler, Bret A.
Engelmayr, George C.
Aikawa, Elena
Bischoff, Joyce
Martin, David P.
Exarhopoulos, Alexis
Moses, Marsha A.
Schoen, Frederick J.
Sacks, Michael S.
Mayer, John E.
author_sort Sales, Virna L.
collection MIT
description Purposes: We investigated whether circulating endothelial progenitor cells (EPCs) can be used as a cell source for the creation of a tissue-engineered heart valve (TEHV). Methods: Trileaflet valved conduits were fabricated using nonwoven polyglycolic acid/poly-4-hydroxybutyrate polymer. Ovine peripheral blood EPCs were dynamically seeded onto a valved conduit and incubated for 7, 14, and 21 days. Results: Before seeding, EPCs were shown to express CD31+, eNOS+, and VE-Cadherin+ but not [alpha]-smooth muscle actin. Histological analysis demonstrated relatively homogenous cellular ingrowth throughout the valved conduit. TEHV constructs revealed the presence of endothelial cell (EC) markers and α-smooth muscle actin+ cells comparable with native valves. Protein levels were comparable with native valves and exceeded those in unseeded controls. EPC-TEHV demonstrated a temporal pattern of matrix metalloproteinases-2/9 expression and tissue inhibitors of metalloproteinase activities comparable to that of native valves. Mechanical properties of EPC-TEHV demonstrated significantly greater stiffness than that of the unseeded scaffolds and native valves. Conclusions: Circulating EPC appears to have the potential to provide both interstitial and endothelial functions and could potentially serve as a single-cell source for construction of autologous heart valves.
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spelling mit-1721.1/621732022-10-01T04:52:42Z Endothelial Progenitor Cells as a Sole Source for Ex Vivo Seeding of Tissue-Engineered Heart Valves Sales, Virna L. Mettler, Bret A. Engelmayr, George C. Aikawa, Elena Bischoff, Joyce Martin, David P. Exarhopoulos, Alexis Moses, Marsha A. Schoen, Frederick J. Sacks, Michael S. Mayer, John E. Harvard University--MIT Division of Health Sciences and Technology Schoen, Frederick J. Schoen, Frederick J. Engelmayr, George C. Purposes: We investigated whether circulating endothelial progenitor cells (EPCs) can be used as a cell source for the creation of a tissue-engineered heart valve (TEHV). Methods: Trileaflet valved conduits were fabricated using nonwoven polyglycolic acid/poly-4-hydroxybutyrate polymer. Ovine peripheral blood EPCs were dynamically seeded onto a valved conduit and incubated for 7, 14, and 21 days. Results: Before seeding, EPCs were shown to express CD31+, eNOS+, and VE-Cadherin+ but not [alpha]-smooth muscle actin. Histological analysis demonstrated relatively homogenous cellular ingrowth throughout the valved conduit. TEHV constructs revealed the presence of endothelial cell (EC) markers and α-smooth muscle actin+ cells comparable with native valves. Protein levels were comparable with native valves and exceeded those in unseeded controls. EPC-TEHV demonstrated a temporal pattern of matrix metalloproteinases-2/9 expression and tissue inhibitors of metalloproteinase activities comparable to that of native valves. Mechanical properties of EPC-TEHV demonstrated significantly greater stiffness than that of the unseeded scaffolds and native valves. Conclusions: Circulating EPC appears to have the potential to provide both interstitial and endothelial functions and could potentially serve as a single-cell source for construction of autologous heart valves. National Institutes of Health (U.S.) (HL-06490) National Institutes of Health (U.S.) (HL-60463) National Institutes of Health (U.S.) (HL-68816) National Institutes of Health (U.S.) (HL-CA83106) National Institutes of Health (U.S.) (P01CA45548) National Institutes of Health (U.S.) (P50DK065298) National Institute of Standards and Technology (U.S.) National Institute of Standards and Technology (U.S.) (grant NANB2H3053) Center for Integration of Medicine and Innovative Technology Gross Cardiovascular Fund American Heart Association (Scientist Development Grant 0635620T) National Institute of Biomedical Imaging and Bioengineering (U.S.) (grant F32 EB003353-01) Ruth L. Kirschstein National Research Service Award American Heart Association (Predoctoral Fellowship 0415406U) 2011-04-08T16:16:57Z 2011-04-08T16:16:57Z 2010-01 Article http://purl.org/eprint/type/JournalArticle 1937-3341 1937-335X http://hdl.handle.net/1721.1/62173 Sales, Virna L. et al. “Endothelial Progenitor Cells as a Sole Source for Ex Vivo Seeding of Tissue-Engineered Heart Valves.” Tissue Engineering Part A 16.1 (2011) : 257-267. ©Mary Ann Liebert, Inc., publishers. en_US http://dx.doi.org/10.1089/ten.tea.2009.0424 Tissue Engineering. Part A Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Mary Ann Liebert, Inc. Mary Ann Liebert
spellingShingle Sales, Virna L.
Mettler, Bret A.
Engelmayr, George C.
Aikawa, Elena
Bischoff, Joyce
Martin, David P.
Exarhopoulos, Alexis
Moses, Marsha A.
Schoen, Frederick J.
Sacks, Michael S.
Mayer, John E.
Endothelial Progenitor Cells as a Sole Source for Ex Vivo Seeding of Tissue-Engineered Heart Valves
title Endothelial Progenitor Cells as a Sole Source for Ex Vivo Seeding of Tissue-Engineered Heart Valves
title_full Endothelial Progenitor Cells as a Sole Source for Ex Vivo Seeding of Tissue-Engineered Heart Valves
title_fullStr Endothelial Progenitor Cells as a Sole Source for Ex Vivo Seeding of Tissue-Engineered Heart Valves
title_full_unstemmed Endothelial Progenitor Cells as a Sole Source for Ex Vivo Seeding of Tissue-Engineered Heart Valves
title_short Endothelial Progenitor Cells as a Sole Source for Ex Vivo Seeding of Tissue-Engineered Heart Valves
title_sort endothelial progenitor cells as a sole source for ex vivo seeding of tissue engineered heart valves
url http://hdl.handle.net/1721.1/62173
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