A High‐Throughput Screening Method to Identify Compounds Displaying Human Vascular Embryonic Toxicity

Rosa, Susana; Pitrez, Patrícia; Fernandes, Hugo; Ferreira, Lino

doi:10.1002/cpsc.93

Title: A High‐Throughput Screening Method to Identify Compounds Displaying Human Vascular Embryonic Toxicity

Journal Article · 26 July 2019 · Current Protocols in Stem Cell Biology

DOI: https://doi.org/10.1002/cpsc.93 · OSTI ID:1545175

Rosa, Susana ^[1]; Pitrez, Patrícia ^[2]; Fernandes, Hugo ^[2]; Ferreira, Lino ^[3]

CNC‐Center for Neurosciences and Cell Biology University of Coimbra Rua Larga Coimbra Portugal
Faculty of Medicine University of Coimbra Health Sciences Campus, Pólo III, Central Unit Coimbra Portugal
CNC‐Center for Neurosciences and Cell Biology University of Coimbra Rua Larga Coimbra Portugal, Faculty of Medicine University of Coimbra Health Sciences Campus, Pólo III, Central Unit Coimbra Portugal

Abstract This article describes a screening platform to identify compounds that affect human embryonic vascular development. The procedure comprises the generation of human embryonic‐like endothelial cells (ECs) from human pluripotent stem cells (hPSCs) and subsequent maturation under arterial flow conditions; the use of these cells for the high‐throughput screening of small molecules that specifically inhibit the survival of embryonic‐like ECs; the confirmation of the hits in embryonic‐like ECs cultured under flow shear stress; and final validation in mouse embryonic ECs. The embryonic‐like ECs express embryonic genes including DLL1 , EPHB2 , LYN , TEK , ID1, NRP2, CAST, FLT1, IGF1, DKK3, NIN, LEF1 , and SORBS3 . The entire screening procedure (without the validation step) can be completed within 1 month. This platform is an alternative/complement to standard animal protocols for assessing the effects of chemicals on embryonic vascular development. © 2019 by John Wiley & Sons, Inc.

View Accepted Manuscript (Publisher)

Cite

Export

Save

Sponsoring Organization:: USDOE

OSTI ID:: 1545175

Journal Information:: Current Protocols in Stem Cell Biology, Journal Name: Current Protocols in Stem Cell Biology Vol. 50 Journal Issue: 1; ISSN 1941-7322

Publisher:: Wiley Blackwell (John Wiley & Sons)Copyright Statement

Country of Publication:: Country unknown/Code not available

Language:: English

References (22)

Disruption of embryonic vascular development in predictive toxicology Knudsen, Thomas B.; Kleinstreuer, Nicole C. Birth Defects Research Part C: Embryo Today: Reviews, Vol. 93, Issue 4 https://doi.org/10.1002/bdrc.20223	journal	December 2011
Enrolling Pregnant Women: Issues in Clinical Research Blehar, Mary C.; Spong, Catherine; Grady, Christine Women's Health Issues, Vol. 23, Issue 1 https://doi.org/10.1016/j.whi.2012.10.003	journal	January 2013
Fair inclusion of pregnant women in clinical trials: an integrated scientific and ethical approach van der Graaf, Rieke; van der Zande, Indira S. E.; den Ruijter, Hester M. Trials, Vol. 19, Issue 1 https://doi.org/10.1186/s13063-017-2402-9	journal	January 2018
High-Throughput Screening for Identification of Blood-Brain Barrier Integrity Enhancers: A Drug Repurposing Opportunity to Rectify Vascular Amyloid Toxicity Qosa, Hisham; Mohamed, Loqman A.; Al Rihani, Sweilem B. Journal of Alzheimer's Disease, Vol. 53, Issue 4 https://doi.org/10.3233/JAD-151179	journal	August 2016
Vascular Progenitor Cells Isolated From Human Embryonic Stem Cells Give Rise to Endothelial and Smooth Muscle–Like Cells and Form Vascular Networks In Vivo Ferreira, Lino S.; Gerecht, Sharon; Shieh, Hester F. Circulation Research, Vol. 101, Issue 3 https://doi.org/10.1161/CIRCRESAHA.107.150201	journal	August 2007
Endothelial potential of human embryonic stem cells Levenberg, Shulamit; Zoldan, Janet; Basevitch, Yaara Blood, Vol. 110, Issue 3 https://doi.org/10.1182/blood-2006-08-019190	journal	August 2007
Thalidomide-induced teratogenesis: History and mechanisms: Thalidomide-Induced Teratogenesis Vargesson, Neil Birth Defects Research Part C: Embryo Today: Reviews, Vol. 105, Issue 2 https://doi.org/10.1002/bdrc.21096	journal	June 2015
The Saga of Thalidomide: Neuropathy to Embryopathy, with Case Reports of Congenital Anomalies Mellin, Gilbert W.; Katzenstein, Michael New England Journal of Medicine, Vol. 267, Issue 23 https://doi.org/10.1056/NEJM196212062672305	journal	December 1962
High-throughput identification of small molecules that affect human embryonic vascular development Vazão, Helena; Rosa, Susana; Barata, Tânia Proceedings of the National Academy of Sciences, Vol. 114, Issue 15 https://doi.org/10.1073/pnas.1617451114	journal	March 2017
Thalidomide Pharmacokinetics and Metabolite Formation in Mice, Rabbits, and Multiple Myeloma Patients Chung, F. Clinical Cancer Research, Vol. 10, Issue 17 https://doi.org/10.1158/1078-0432.CCR-04-0421	journal	September 2004
Identification and propagation of haploid human pluripotent stem cells Sagi, Ido; Egli, Dieter; Benvenisty, Nissim Nature Protocols, Vol. 11, Issue 11 https://doi.org/10.1038/nprot.2016.145	journal	October 2016
Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation Therapontos, C.; Erskine, L.; Gardner, E. R. Proceedings of the National Academy of Sciences, Vol. 106, Issue 21 https://doi.org/10.1073/pnas.0901505106	journal	May 2009
Phenotype-based high-content chemical library screening identifies statins as inhibitors of in vivo lymphangiogenesis Schulz, M. M. P.; Reisen, F.; Zgraggen, S. Proceedings of the National Academy of Sciences, Vol. 109, Issue 40 https://doi.org/10.1073/pnas.1206036109	journal	September 2012
Differentiation, Evaluation, and Application of Human Induced Pluripotent Stem Cell–Derived Endothelial Cells Lin, Yang; Gil, Chang-Hyun; Yoder, Mervin C. Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 37, Issue 11 https://doi.org/10.1161/ATVBAHA.117.309962	journal	November 2017
Expansion and maintenance of human embryonic stem cell–derived endothelial cells by TGFβ inhibition is Id1 dependent James, Daylon; Nam, Hyung-song; Seandel, Marco Nature Biotechnology, Vol. 28, Issue 2 https://doi.org/10.1038/nbt.1605	journal	January 2010
Environmental Impact on Vascular Development Predicted by High-Throughput Screening Kleinstreuer, Nicole C.; Judson, Richard S.; Reif, David M. Environmental Health Perspectives, Vol. 119, Issue 11 https://doi.org/10.1289/ehp.1103412	journal	November 2011
Ligament tissue engineering: An evolutionary materials science approach Laurencin, Cato T.; Freeman, Joseph W. Biomaterials, Vol. 26, Issue 36 https://doi.org/10.1016/j.biomaterials.2005.05.073	journal	December 2005
Thymosin β4 induces adult epicardial progenitor mobilization and neovascularization Smart, Nicola; Risebro, Catherine A.; Melville, Athalie A. D. Nature, Vol. 445, Issue 7124 https://doi.org/10.1038/nature05383	journal	November 2006
Cognitive function in young adults following intrauterine growth restriction with abnormal fetal aortic blood flow Tideman, E.; Maršál, K.; Ley, D. Ultrasound in Obstetrics and Gynecology, Vol. 29, Issue 6 https://doi.org/10.1002/uog.4042	journal	January 2007
Anterior cruciate ligament- and hamstring tendon-derived cells: in vitro differential properties of cells involved in ACL reconstruction : Differential properties of cells involved in ACL reconstruction Ghebes, Corina Adriana; Kelder, Cindy; Schot, Thomas Journal of Tissue Engineering and Regenerative Medicine, Vol. 11, Issue 4 https://doi.org/10.1002/term.2009	journal	March 2015
Thymosin β4 and the vasculature: multiple roles in development, repair and protection against disease Dubé, Karina N.; Smart, Nicola Expert Opinion on Biological Therapy, Vol. 18, Issue sup1 https://doi.org/10.1080/14712598.2018.1459558	journal	May 2018
Generation of Induced Pluripotent Stem Cells from Human Cord Blood Haase, Alexandra; Olmer, Ruth; Schwanke, Kristin Cell Stem Cell, Vol. 5, Issue 4 https://doi.org/10.1016/j.stem.2009.08.021	journal	October 2009

Similar Records

Generation of H1 PAX6WT/EGFP reporter cells to purify PAX6 positive neural stem/progenitor cells

Journal Article · 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23136960

Wu, Wei; Liu, Juli; Su, Zhenghui; +5 more

Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

Journal Article · 2015 · Biochemical and Biophysical Research Communications · OSTI ID:22592829

Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.; +6 more

Distinct expression patterns of Flk1 and Flt1 in the coronary vascular system during development and after myocardial infarction

Journal Article · 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23127539

Kurotsu, Shota; Osakabe, Rina; Isomi, Mari; +3 more

Title: A High‐Throughput Screening Method to Identify Compounds Displaying Human Vascular Embryonic Toxicity

Citation Formats

References (22)

Similar Records

Related Subjects