Ethical, legal, regulatory, and policy issues concerning embryoids: a systematic review of the literature DOI Creative Commons
Ana S. Iltis,

Grace Koster,

Emily Reeves

et al.

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 21, 2023

Abstract Recent advances in methods to culture pluripotent stem cells model human development have resulted entities that increasingly recapitulated advanced stages of early embryo development. These entities, referred by numerous terms such as embryoids, are becoming more sophisticated and could resemble embryos ever closely research progresses. This paper reports a systematic review the ethical, legal, regulatory, policy questions concerns found literature concerning embryoid published from 2016 2022. We identified 56 papers use 53 distinct names or refer embryoids four broad categories considerations literature: justifications/benefits, ethical significance moral status, permissible use, regulatory oversight challenges. Analyzing full range issues is critical step toward fostering robust social implications this emerging area developing appropriate oversight.

Language: Английский

Controlled modelling of human epiblast and amnion development using stem cells DOI
Yi Zheng, Xufeng Xue, Yue Shao

et al.

Nature, Journal Year: 2019, Volume and Issue: 573(7774), P. 421 - 425

Published: Sept. 11, 2019

Language: Английский

Citations

405
Mechanisms of early placental development in mouse and humans DOI
Myriam Hemberger, Courtney W. Hanna, Wendy Dean

et al.

Nature Reviews Genetics, Journal Year: 2019, Volume and Issue: 21(1), P. 27 - 43

Published: Sept. 18, 2019

Language: Английский

Citations

380
Human blastoids model blastocyst development and implantation DOI Creative Commons
Harunobu Kagawa, Alok Javali, Heidar Heidari Khoei

et al.

Nature, Journal Year: 2021, Volume and Issue: 601(7894), P. 600 - 605

Published: Dec. 2, 2021

Abstract One week after fertilization, human embryos implant into the uterus. This event requires embryo to form a blastocyst consisting of sphere encircling cavity lodging proper. Stem cells can model that we called blastoid 1 . Here show naive pluripotent stem cultured in PXGL medium 2 and triply inhibited for Hippo, TGF-β ERK pathways efficiently (with more than 70% efficiency) blastoids generating blastocyst-stage analogues three founding lineages (more 97% trophectoderm, epiblast primitive endoderm) according sequence timing development. Blastoids spontaneously first axis, observe induces local maturation polar thereby endowing with capacity directionally attach hormonally stimulated endometrial cells, as during implantation. Thus, propose such is faithful, scalable ethical investigating implantation development 3,4

Language: Английский

Citations

327
Self-organization of stem cells into embryos: A window on early mammalian development DOI Open Access
Marta N. Shahbazi, Eric D. Siggia, Magdalena Zernicka‐Goetz

et al.

Science, Journal Year: 2019, Volume and Issue: 364(6444), P. 948 - 951

Published: June 6, 2019

Embryonic development is orchestrated by robust and complex regulatory mechanisms acting at different scales of organization. In vivo studies are particularly challenging for mammals after implantation, owing to the small size inaccessibility embryo. The generation stem cell models embryo represents a powerful system with which dissect this complexity. Control geometry, modulation physical environment, priming chemical signals reveal intrinsic capacity embryonic cells make patterns. Adding extraembryonic lineages generates three-dimensional that more autonomous from environment recapitulate many features pre- postimplantation mouse embryo, including gastrulation. Here, we review principles self-organization how they set in motion create an

Language: Английский

Citations

185
Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells DOI Creative Commons
Gaël Castel, Dimitri Meistermann,

Betty Bretin

et al.

Cell Reports, Journal Year: 2020, Volume and Issue: 33(8), P. 108419 - 108419

Published: Nov. 1, 2020

Human trophoblast stem cells (hTSCs) derived from blastocysts and first-trimester cytotrophoblasts offer an unprecedented opportunity to study the placenta. However, access human embryos placentas is limited, thus preventing establishment of hTSCs diverse genetic backgrounds associated with placental disorders. Here, we show that can be generated numerous using post-natal via two alternative methods: (1) somatic cell reprogramming adult fibroblasts OCT4, SOX2, KLF4, MYC (OSKM) (2) fate conversion naive extended pluripotent cells. The resulting induced/converted recapitulated hallmarks including long-term self-renewal, expression specific transcription factors, transcriptomic signature, potential differentiate into syncytiotrophoblast extravillous We also clarified developmental stage these resemble day 8 cytotrophoblasts. Altogether, hTSC lines origins open possibility model both development diseases in a dish.

Language: Английский

Citations

149
Organoids: a systematic review of ethical issues DOI Creative Commons
Dide de Jongh, Emma K. Massey, Ekaterine Berishvili

et al.

Stem Cell Research & Therapy, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 23, 2022

Abstract Organoids are 3D structures grown from pluripotent stem cells derived human tissue and serve as in vitro miniature models of organs. expected to revolutionize biomedical research clinical care. However, organoids not seen morally neutral. For instance, donors may perceive enduring personal connections with their organoids, setting higher bars for informed consent patient participation. Also, several organoid sub-types, e.g., brain human–animal chimeric have raised controversy. This systematic review provides an overview ethical discussions conducted the scientific literature on organoids. The covers both applications technology discusses topics consent, commercialization, personalized medicine, transplantation, chimeras, gastruloids. It shows that further is needed especially help ensure responsible development implementation this field.

Language: Английский

Citations

104
An ethical framework for human embryology with embryo models DOI Creative Commons
Nicolas Rivron, Alfonso Martínez Arias, Martín F. Pera

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(17), P. 3548 - 3557

Published: Aug. 1, 2023

A human embryo's legal definition and its entitlement to protection vary greatly worldwide. Recently, pluripotent stem cells have been used form in vitro models of early embryos that challenged definitions raised questions regarding their usage. In this light, we propose a refined an embryo, suggest "tipping points" for when embryo could eventually be afforded similar embryos, then revisit basic ethical principles might help draft roadmap the gradual, justified usage manner aims maximize benefits society.

Language: Английский

Citations

55
Stem-cell-based embryo models for fundamental research and translation DOI
Jianping Fu, Aryeh Warmflash, Matthias P. Lütolf

et al.

Nature Materials, Journal Year: 2020, Volume and Issue: 20(2), P. 132 - 144

Published: Nov. 16, 2020

Language: Английский

Citations

134
Human embryo research, stem cell-derived embryo models and in vitro gametogenesis: Considerations leading to the revised ISSCR guidelines DOI Creative Commons
Amander T. Clark, Ali H. Brivanlou, Jianping Fu

et al.

Stem Cell Reports, Journal Year: 2021, Volume and Issue: 16(6), P. 1416 - 1424

Published: May 27, 2021

The ISSCR Guidelines for Stem Cell Research and Clinical Translation were last revised in 2016. Since then, rapid progress has been made research areas related to vitro culture of human embryos, creation stem cell-based embryo models, gametogenesis. Therefore, a working group international experts was convened review the oversight process provide an update guidelines. This report captures discussion summarizes major recommendations by this group, with specific emphasis on updating categories engagement specialized scientific ethical process.

Language: Английский

Citations

95
3D gastruloids: a novel frontier in stem cell-based in vitro modeling of mammalian gastrulation DOI Creative Commons
Susanne C. van den Brink, Alexander van Oudenaarden

Trends in Cell Biology, Journal Year: 2021, Volume and Issue: 31(9), P. 747 - 759

Published: July 22, 2021

3D gastruloids, aggregates of embryonic stem cells that recapitulate key aspects gastrula-stage embryos, have emerged as a powerful tool to study the early stages mammalian post-implantation development in vitro. Owing their tractable nature and relative ease by which they can be generated large numbers, gastruloids provide an unparalleled opportunity normal pathological embryogenesis from bottom-up perspective high-throughput manner. Here, we review how gastruloid models exploited deepen our understanding development. In addition, discuss current limitations, potential clinical applications, ethical implications this emerging model system.

Language: Английский

Citations

90