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

Hans-Werner Denker

doi:10.3390/cells10061461

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.

Highlights

Rossant and Tam [6] have more recently proposed addressing such constructs with the general term “stem cell-based embryo models“, and to group them into two categories in order to emphasize aspects of potential viability, these two groups differing in their completeness, with or without extraembryonic cell types: (1) “integrated stem cell-based embryo models” would possess derivatives of the extraembryonic cell types, while (2) “non-integrated stem cell-based embryo models“ lack these extraembryonic cell types
What does all this tell us with regard to ethical implications arising when these embryoid formation technologies are applied with human stem cells? Undifferentiated
As discussed, groups of pluripotent stem cells (PPSC) can gain developmental autonomy in the process that is usually addressed as selforganization, either on an organ level or an early embryo level, depending on the epigenetic state of the initiating stem cells and on the local conditions provided in culture

Summary

Introduction

The call for initiating a broad discussion on the ethical implications gained momentum when, in more recent years, methodologies were presented that allowed culture of real embryos (cleavage stages or blastocysts) up to post-implantation stages [16,17] This was followed by studies which showed that when such improved methodologies were used for stem cell culturing, embryoids could be formed more regularly, and that some of these constructs could develop into complex structures which may come close to resembling, e.g., primitive streak or even more advanced stages (gastruloids), in the mouse model as well as in the human [18,19,20,21,22,23,24,25,26,27,28,29,30]. In order to put this into context, let us first briefly summarize some relevant facts about the morphogenesis of real mammalian embryos

Some Relevant Facts about Mammalian Embryogenesis

Autonomy in the Morphogenesis of Stem Cell-Derived Embryoids

Spontaneous Budding of Blastocyst-Like Cysts in Stem Cell Cultures

Conclusions and Ethical Implications

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