Bioengineered microenvironment to culture early embryos

Gu, Zhen; Guo, Jia; Wang, Hongmei; Wen, Yongqiang; Gu, Qi

doi:10.1111/cpr.12754

Cited by 11 publications

(6 citation statements)

References 126 publications

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“…In 2016, two studies demonstrated growing human embryos in the lab for 13 days after fertilization, and further culturing has been suspended based on ethical issues rather than technological infeasibility (Deglincerti et al, 2016 ; Shahbazi et al, 2016 ), which raised valid concerns regarding the 14-day rule in hindering the development of embryonic research (Regalado, 2021 ). Moreover, the reports of culturing non-human primate embryos in vitro up to 20 days after fertilization and of a platform to support in vitro cultured mouse embryos to early organogenesis stages, in 2019 and 2020 respectively (Ma et al, 2019 ; Niu et al, 2019 ; Gu et al, 2020 ), have raised technological feasibility to grow human embryos in the lab beyond 14 days using methods adapted from their work if the 14-day rule does not stand in the way. This has further unleashed impressive pressure on the review of the 14-day rule.…”

Section: The Technologymentioning

confidence: 99%

A framework for the responsible reform of the 14-day rule in human embryo research

Peng

Xiao

et al. 2022

Protein Cell

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Ever since the world's first "test-tube" baby was born in 1978, the use of human embryos in research has become highly controversial ethically and thus created a significant challenge for jurisdictions, especially in Europe and the United States, to determine the relevant policies (Poplawski and Gillett, 1991). To resolve the dispute and responsibly promote human embryonic research, the 14-day rule, which prohibits culturing human embryos in vitro beyond 14 days or the onset of primitive streak, was proposed over 40 years ago (Hyun et al., 2016). This rule has become a widely accepted bioethical norm and has been introduced into laws or guidelines by many jurisdictions, such as the United Kingdom, Australia, and China (Matthews et al., 2020). However, recent scientific advancements and policy debates have put this rule under increasing strain. Particularly, the major revision to the 14-day rule proposed by the International Society for Stem Cell Research (ISSCR) latest updated guidelines has fuelled heated debates and raised concerns worldwide (International Society for Stem Cell Research, 2021).For China, whose scientific concerns, traditional culture, and religion are largely different from the West, the debates and challenges are different and somewhat unique. Thus, it is essential to present a responsible and coordinated way, suitable for Chinese ethical and cultural values and public acceptance, to cope with the potential adjustment of the 14-day rule and to promote the development of the entire embryo research endeavor in China. We first explore recent advances in embryonic and pertinent research fields that directly or indirectly challenge the 14-day rule. Within this context, we then evaluate the overall ethical controversies worldwide and the recent public debate on the 14-day rule in China. Separately, we discuss China's regulatory framework for human embryo research, including the 14-day rule. On this basis, we lastly provide an essential coordinated framework and strategies to deal with the possible changes to the 14-day rule based on China-specific conditions. We hope that this discussion helps both China and other countries establish a framework of mutual respect, win-win cooperation, and responsibility for future embryo research.

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Section: The Technologymentioning

confidence: 99%

A framework for the responsible reform of the 14-day rule in human embryo research

Peng

Xiao

et al. 2022

Protein Cell

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“…The impact from extracellular matrices should not be underestimated even if embryos are non-adherent. The third direction is to leverage the current microfabrication technologies, including lithography, 3D printing, and laser cutting, to fabricate integrated microdevices with biosensing components to monitor levels of O 2 , pH and growth factors in real-time, as well as relevant biophysical cues (see recent review by (Gu et al, 2020)). Altogether, the next-generation embryo culture systems need to be designed based on mechanobiology principles and allow full control of the biophysical and biochemical microenvironment of embryos.…”

Section: Conclusion and Further Questionsmentioning

confidence: 99%

Biophysical optimization of preimplantation embryo culture: what mechanics can offer ART

Hawkins

Miao

Cui

et al. 2021

Molecular Human Reproduction

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Owing to the rise of ART and mounting reports of epigenetic modification associated with them, an understanding of optimal embryo culture conditions and reliable indicators of embryo quality are highly sought after. There is a growing body of evidence that mechanical biomarkers can rival embryo morphology as an early indicator of developmental potential and that biomimetic mechanical cues can promote healthy development in preimplantation embryos. This review will summarize studies that investigate the role of mechanics as both indicators and promoters of mammalian preimplantation embryo development and evaluate their potential for improving future embryo culture systems.

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“…Epithelium-trophectoderm adhesion and interaction is the initiated stage of implantation. However, there were few reports describing the maternal-fetal interface using the ex-vivo long-term culture system [29][30][31][32] . We investigated whether there was invasion of embryos into the U3N system through confocal imaging of the embryos and the substrates.…”

Section: Interactions Between Peri-implantation Mouse Embryos and Utementioning

confidence: 99%

A uterus-inspired 3D niche drives embryo development beyond implantation

Gu¹,

Guo²,

Zhai³

et al. 2020

Preprint

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The mammalian embryo must undergo dramatic morphogenetic changes to invade the uterine endometrium and achieve implantation. Thus, recapitulation of implantation using in vitro systems is crucial for revealing the mechanisms controlling early development and the main problems compromising human fertility. Experimental systems based on two-dimensional (2D) platforms cannot fully recapitulate the in vivo 3D microenvironments of the embryo. Therefore, here we use collagen grafted onto polydimethylsiloxane (PDMS) based on the uterine mechanics and microstructure to establish a uterus-inspired 3D niche (U3N). Our U3N enables mouse embryos to form egg cylinders at high rate and reach the developmental stages of heartbeat. Moreover, a unique interface forms between the embryo and collagen, showing the invasion of trophoblasts into collagen fires, which simulate the developmental process of implantation. Our findings highlight embryo-substrate interaction as a key characteristic of post-implantation development in vitro and as an important design parameter of 3D conditions for embryo culture.

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Bioengineered microenvironment to culture early embryos

Cited by 11 publications

References 126 publications

A framework for the responsible reform of the 14-day rule in human embryo research

A framework for the responsible reform of the 14-day rule in human embryo research

Biophysical optimization of preimplantation embryo culture: what mechanics can offer ART

A uterus-inspired 3D niche drives embryo development beyond implantation

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