Human Teratoma-Derived Hematopoiesis Is a Highly Polyclonal Process Supported by Human Umbilical Vein Endothelial Cells
Summary: Hematopoietic stem cells (HSCs) ensure a life-long regeneration of the blood system and are therefore an important source for transplantation and gene therapy. The teratoma environment supports the complex development of functional HSCs from human pluripotent stem cells, which is difficult...
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Format: | Article |
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Elsevier
2018-11-01
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Series: | Stem Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671118303953 |
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doaj-8106813214384656a4a7ca4fb6cb1c6a |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Friederike Philipp Anton Selich Michael Rothe Dirk Hoffmann Susanne Rittinghausen Michael A. Morgan Denise Klatt Silke Glage Stefan Lienenklaus Vanessa Neuhaus Katherina Sewald Armin Braun Axel Schambach |
spellingShingle |
Friederike Philipp Anton Selich Michael Rothe Dirk Hoffmann Susanne Rittinghausen Michael A. Morgan Denise Klatt Silke Glage Stefan Lienenklaus Vanessa Neuhaus Katherina Sewald Armin Braun Axel Schambach Human Teratoma-Derived Hematopoiesis Is a Highly Polyclonal Process Supported by Human Umbilical Vein Endothelial Cells Stem Cell Reports |
author_facet |
Friederike Philipp Anton Selich Michael Rothe Dirk Hoffmann Susanne Rittinghausen Michael A. Morgan Denise Klatt Silke Glage Stefan Lienenklaus Vanessa Neuhaus Katherina Sewald Armin Braun Axel Schambach |
author_sort |
Friederike Philipp |
title |
Human Teratoma-Derived Hematopoiesis Is a Highly Polyclonal Process Supported by Human Umbilical Vein Endothelial Cells |
title_short |
Human Teratoma-Derived Hematopoiesis Is a Highly Polyclonal Process Supported by Human Umbilical Vein Endothelial Cells |
title_full |
Human Teratoma-Derived Hematopoiesis Is a Highly Polyclonal Process Supported by Human Umbilical Vein Endothelial Cells |
title_fullStr |
Human Teratoma-Derived Hematopoiesis Is a Highly Polyclonal Process Supported by Human Umbilical Vein Endothelial Cells |
title_full_unstemmed |
Human Teratoma-Derived Hematopoiesis Is a Highly Polyclonal Process Supported by Human Umbilical Vein Endothelial Cells |
title_sort |
human teratoma-derived hematopoiesis is a highly polyclonal process supported by human umbilical vein endothelial cells |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2018-11-01 |
description |
Summary: Hematopoietic stem cells (HSCs) ensure a life-long regeneration of the blood system and are therefore an important source for transplantation and gene therapy. The teratoma environment supports the complex development of functional HSCs from human pluripotent stem cells, which is difficult to recapitulate in culture. This model mimics various aspects of early hematopoiesis, but is restricted by the low spontaneous hematopoiesis rate. In this study, a feasible protocol for robust hematopoiesis has been elaborated. We achieved a significant increase of the teratoma-derived hematopoietic population when teratomas were generated in the NSGS mouse, which provides human cytokines, together with co-injection of human umbilical vein endothelial cells. Since little is known about hematopoiesis in teratomas, we addressed localization and clonality of the hematopoietic lineage. Our results indicate that early human hematopoiesis is closely reflected in teratoma formation, and thus highlight the value of this model. : Schambach and colleagues show evidence that hematopoiesis in hiPSC-derived teratomas occurs by endothelial-to-hematopoietic transition in a highly polyclonal manner. This process was supported by the presence of HUVECs in the NSGS mouse, which provides human SCF, IL-3, and GM-CSF. The established hematopoiesis model can potentially be used for disease modeling and improvement of hematopoietic differentiation protocols. Keywords: hematopoiesis, teratoma, hiPSC, EHT, genetic barcoding, HUVECs, embryogenesis |
url |
http://www.sciencedirect.com/science/article/pii/S2213671118303953 |
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doaj-8106813214384656a4a7ca4fb6cb1c6a2020-11-24T21:48:27ZengElsevierStem Cell Reports2213-67112018-11-0111510511060Human Teratoma-Derived Hematopoiesis Is a Highly Polyclonal Process Supported by Human Umbilical Vein Endothelial CellsFriederike Philipp0Anton Selich1Michael Rothe2Dirk Hoffmann3Susanne Rittinghausen4Michael A. Morgan5Denise Klatt6Silke Glage7Stefan Lienenklaus8Vanessa Neuhaus9Katherina Sewald10Armin Braun11Axel Schambach12Institute of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Straße1, 30625 Hannover, Germany; Fraunhofer Institute for Toxicology and Experimental Medicine, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, GermanyInstitute of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Straße1, 30625 Hannover, GermanyInstitute of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Straße1, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, GermanyInstitute of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Straße1, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, GermanyFraunhofer Institute for Toxicology and Experimental Medicine, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany; German Centre for Lung Research DZL, Hannover, GermanyInstitute of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Straße1, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, GermanyInstitute of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Straße1, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, GermanyInstitute for Laboratory Animal Science, Hannover Medical School, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, GermanyInstitute for Laboratory Animal Science, Hannover Medical School, 30625 Hannover, GermanyFraunhofer Institute for Toxicology and Experimental Medicine, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany; German Centre for Lung Research DZL, Hannover, GermanyFraunhofer Institute for Toxicology and Experimental Medicine, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany; German Centre for Lung Research DZL, Hannover, GermanyFraunhofer Institute for Toxicology and Experimental Medicine, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany; German Centre for Lung Research DZL, Hannover, GermanyInstitute of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Straße1, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Corresponding authorSummary: Hematopoietic stem cells (HSCs) ensure a life-long regeneration of the blood system and are therefore an important source for transplantation and gene therapy. The teratoma environment supports the complex development of functional HSCs from human pluripotent stem cells, which is difficult to recapitulate in culture. This model mimics various aspects of early hematopoiesis, but is restricted by the low spontaneous hematopoiesis rate. In this study, a feasible protocol for robust hematopoiesis has been elaborated. We achieved a significant increase of the teratoma-derived hematopoietic population when teratomas were generated in the NSGS mouse, which provides human cytokines, together with co-injection of human umbilical vein endothelial cells. Since little is known about hematopoiesis in teratomas, we addressed localization and clonality of the hematopoietic lineage. Our results indicate that early human hematopoiesis is closely reflected in teratoma formation, and thus highlight the value of this model. : Schambach and colleagues show evidence that hematopoiesis in hiPSC-derived teratomas occurs by endothelial-to-hematopoietic transition in a highly polyclonal manner. This process was supported by the presence of HUVECs in the NSGS mouse, which provides human SCF, IL-3, and GM-CSF. The established hematopoiesis model can potentially be used for disease modeling and improvement of hematopoietic differentiation protocols. Keywords: hematopoiesis, teratoma, hiPSC, EHT, genetic barcoding, HUVECs, embryogenesishttp://www.sciencedirect.com/science/article/pii/S2213671118303953 |