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Stem Cells Dev. 2019 Aug 9. doi: 10.1089/scd.2018.0246. [Epub ahead of print]

Vascular Cells and Tissue Constructs Derived from Human Pluripotent Stem Cells for Toxicological Screening.

Author information

1
Institute of Medical Biology, 172636, Singapore, Singapore; drew@scaledbiolabs.com.
2
Institute of Medical Biology, 172636, Singapore, Singapore; victor.nurcombe@imb.a-star.edu.sg.
3
Lee Kong Chian School of Medicine, Nanyang Technological University-Imperial College London, Singapore.
4
Institute of Molecular and Cell Biology, Singapore, Singapore; ccheung@ntu.edu.sg.
5
Institute of Medical Biology, 172636, Singapore, Singapore.
6
National University Singapore Yong Loo Lin School of Medicine, 63751, Department of Orthopaedic Surgery, Singapore, Singapore; simon.cool@imb.a-star.edu.sg.

Abstract

The ability of human stem cells to generate somatic cell lineages makes them ideal candidates for use in toxicological testing and eventually, pre-clinical drug development. Such resources would support an evolution away from human primary cells or research animal models, which suffer from variability and poor predictability, towards off-the-shelf assays of chemical toxicity and drug efficacy using human cells and tissues. To this end, we generated vascular cell populations (smooth muscle cells and endothelial cells) from human pluripotent stem cells (hPSC), arranged them into 3D co-cultures within supportive gel matrices, and directed their propensity for self-organisation resembling microvasculature. The resulting vascular cell populations and co-cultured constructs were then arrayed in high-throughput and used for screening a library of environmental and clinical chemical agents for immunological and toxicological responses. The screen effectively stratified the chemicals into various levels of toxicity, with both cell type-specific, and co-culture-dependent responses observed. Thus, hPSC-derived vascular cells and constructs could be progressed further towards use in toxicant and drug screening.

PMID:
31397206
DOI:
10.1089/scd.2018.0246

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