Reproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates.

<h4>Background</h4>Human embryonic stem cells (hESC) should enable novel insights into early human development and provide a renewable source of cells for regenerative medicine. However, because the three-dimensional hESC aggregates [embryoid bodies (hEB)] typically employed to reveal hE...

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Autores principales:	Mark D Ungrin, Chirag Joshi, Andra Nica, Céline Bauwens, Peter W Zandstra
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dec850753f5f4ca390e5baddc5fc9cdc
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spelling	oai:doaj.org-article:dec850753f5f4ca390e5baddc5fc9cdc2021-11-25T06:13:26ZReproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates.1932-620310.1371/journal.pone.0001565https://doaj.org/article/dec850753f5f4ca390e5baddc5fc9cdc2008-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18270562/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Human embryonic stem cells (hESC) should enable novel insights into early human development and provide a renewable source of cells for regenerative medicine. However, because the three-dimensional hESC aggregates [embryoid bodies (hEB)] typically employed to reveal hESC developmental potential are heterogeneous and exhibit disorganized differentiation, progress in hESC technology development has been hindered.<h4>Methodology/principal findings</h4>Using a centrifugal forced-aggregation strategy in combination with a novel centrifugal-extraction approach as a foundation, we demonstrated that hESC input composition and inductive environment could be manipulated to form large numbers of well-defined aggregates exhibiting multi-lineage differentiation and substantially improved self-organization from single-cell suspensions. These aggregates exhibited coordinated bi-domain structures including contiguous regions of extraembryonic endoderm- and epiblast-like tissue. A silicon wafer-based microfabrication technology was used to generate surfaces that permit the production of hundreds to thousands of hEB per cm(2).<h4>Conclusions/significance</h4>The mechanisms of early human embryogenesis are poorly understood. We report an ultra high throughput (UHTP) approach for generating spatially and temporally synchronised hEB. Aggregates generated in this manner exhibited aspects of peri-implantation tissue-level morphogenesis. These results should advance fundamental studies into early human developmental processes, enable high-throughput screening strategies to identify conditions that specify hESC-derived cells and tissues, and accelerate the pre-clinical evaluation of hESC-derived cells.Mark D UngrinChirag JoshiAndra NicaCéline BauwensPeter W ZandstraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 2, p e1565 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mark D Ungrin Chirag Joshi Andra Nica Céline Bauwens Peter W Zandstra Reproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates.
description	<h4>Background</h4>Human embryonic stem cells (hESC) should enable novel insights into early human development and provide a renewable source of cells for regenerative medicine. However, because the three-dimensional hESC aggregates [embryoid bodies (hEB)] typically employed to reveal hESC developmental potential are heterogeneous and exhibit disorganized differentiation, progress in hESC technology development has been hindered.<h4>Methodology/principal findings</h4>Using a centrifugal forced-aggregation strategy in combination with a novel centrifugal-extraction approach as a foundation, we demonstrated that hESC input composition and inductive environment could be manipulated to form large numbers of well-defined aggregates exhibiting multi-lineage differentiation and substantially improved self-organization from single-cell suspensions. These aggregates exhibited coordinated bi-domain structures including contiguous regions of extraembryonic endoderm- and epiblast-like tissue. A silicon wafer-based microfabrication technology was used to generate surfaces that permit the production of hundreds to thousands of hEB per cm(2).<h4>Conclusions/significance</h4>The mechanisms of early human embryogenesis are poorly understood. We report an ultra high throughput (UHTP) approach for generating spatially and temporally synchronised hEB. Aggregates generated in this manner exhibited aspects of peri-implantation tissue-level morphogenesis. These results should advance fundamental studies into early human developmental processes, enable high-throughput screening strategies to identify conditions that specify hESC-derived cells and tissues, and accelerate the pre-clinical evaluation of hESC-derived cells.
format	article
author	Mark D Ungrin Chirag Joshi Andra Nica Céline Bauwens Peter W Zandstra
author_facet	Mark D Ungrin Chirag Joshi Andra Nica Céline Bauwens Peter W Zandstra
author_sort	Mark D Ungrin
title	Reproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates.
title_short	Reproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates.
title_full	Reproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates.
title_fullStr	Reproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates.
title_full_unstemmed	Reproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates.
title_sort	reproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/dec850753f5f4ca390e5baddc5fc9cdc
work_keys_str_mv	AT markdungrin reproducibleultrahighthroughputformationofmulticellularorganizationfromsinglecellsuspensionderivedhumanembryonicstemcellaggregates AT chiragjoshi reproducibleultrahighthroughputformationofmulticellularorganizationfromsinglecellsuspensionderivedhumanembryonicstemcellaggregates AT andranica reproducibleultrahighthroughputformationofmulticellularorganizationfromsinglecellsuspensionderivedhumanembryonicstemcellaggregates AT celinebauwens reproducibleultrahighthroughputformationofmulticellularorganizationfromsinglecellsuspensionderivedhumanembryonicstemcellaggregates AT peterwzandstra reproducibleultrahighthroughputformationofmulticellularorganizationfromsinglecellsuspensionderivedhumanembryonicstemcellaggregates
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Reproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates.

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