Autonomy in the Development of Stem Cell-Derived Embryoids: Sprouting Blastocyst-Like Cysts, and Ethical Implications

Abstract

The experimental production of complex structures resembling mammalian embryos (e.g., blastoids, gastruloids) from pluripotent stem cells in vitro has become a booming research field. Since some of these embryoid models appear to reach a degree of complexity that may come close to viability, a broad discussion has set in with the aim to arrive at a consensus on the ethical implications with regard to acceptability of the use of this technology with human cells. The present text focuses on aspects of the gain of organismic wholeness of such stem cell-derived constructs, and of autonomy of self-organization, raised by recent reports on blastocyst-like cysts spontaneously budding in mouse stem cell cultures, and by previous reports on likewise spontaneous formation of gastrulating embryonic disc-like structures in primate models. Mechanisms of pattern (axis) formation in early embryogenesis are discussed in the context of self-organization of stem cell clusters. It is concluded that ethical aspects of development of organismic wholeness in the formation of embryoids need to receive more attention in the present discussions about new legal regulations in this field.

Organoids: a systematic review of ethical issues

“…Sixteen papers mentioned the ethical acceptability of the usage of gastruloids in research [ 27 , 30 , 42 , 51 , 58 , 62 , 63 , 73 , 79 , 80 , 82 , 102 – 105 ]. Gastruloids constitute a sub-type of organoids, but they are distinct because they do not copy organs but rather early developmental processes [ 58 , 63 , 103 , 104 ].…”

“…Gastruloids constitute a sub-type of organoids, but they are distinct because they do not copy organs but rather early developmental processes [ 58 , 63 , 103 , 104 ]. Gastruloids are somewhat similar to human embryos, because they contain elements of the primitive streak formation and cells from each of the three germ layers, and they recapitulate aspects of early embryogenesis in vitro [ 63 , 103 – 105 ], though their morphology is somewhat different [ 104 ]. Research with gastruloids could provide insights into early human embryo development, species–species differences, and disorders associated with first-trimester pregnancy and miscarriage [ 42 , 58 , 63 , 103 , 104 ].…”

“…To date, ethical concerns have been brought to the fore regarding the moral status that could be attributed to gastruloids [ 42 , 46 , 58 , 62 , 63 , 68 , 73 , 82 , 103 – 105 ], and the extent to which gastruloids may be permitted to mature [ 58 , 63 , 68 , 73 , 102 – 105 ]. The discussion ties in with the long-standing debate about the morality of creating human embryos or ‘early human life’ in vitro.…”

“…Furthermore, in discussions on the extent to which gastruloids may be permitted to mature, reference is often made to the internationally well-accepted 14-day rule [ 58 , 63 , 68 , 73 , 104 , 105 ]. This rule is endorsed by the Warnock committee in 1982 and limits researchers to culture human embryos for 14 days of development in vitro.…”

The closer the knit, the tighter the fit: conceptual and ethical issues of human embryo modelling

“…From an ethical perspective, this would mean more room for human embryo research, including research beyond the 14 days that legislation currently allows. But the case against potentiality remains an issue for further analysis and debate (Hyun, 2013), with some authors conversely arguing that ELS-research may precisely demonstrate a stem cell capacity to initiate autonomous development under the right conditions (Denker, 2021). Supposing, for the sake of argument, that the potentiality argument withstands, two side notes are still worth making.…”