6 March 2017
Artificial mouse embryo developed in vitro
A structure whose composition and architecture very closely resemble a mouse embryo has been developed in vitro by scientists in the UK. Reporting their study in the journal Science, Professor Zernicka-Goetz and colleagues at the University of Cambridge describe how, using a combination of mouse embryonic and trophoblast stem cells, together with a 3D scaffold referred to an "extracellular matrix", they were able to grow a structure capable of assembling itself as a natural embryo.(1) After five days, the embryos resembled normal mouse embryos about to start their differentiation into various body tissues and organs.
Both the embryonic and extra-embryonic cells appeared to communicate and become organised into a structure that looked like and behaved like an embryo. "It has anatomically correct regions that develop in the right place and at the right time," explained Zernicka-Goetz in a press statement. "In a sense, the cells are telling each other where in the embryo to place themselves."
The investigators claim that the study demonstrates the ability of distinct stem cell types (a single embryonic and a cluster of trophoblast) to self-assemble in vitro to generate embryos whose morphogenesis, architecture and constituent cell-types resemble natural embryos. The culture system allowed interaction of these stem cells within a three-dimensional scaffold of extra-cellular matrix. "We found that in these culture conditions ESCs and TSCs developed into an elongated cylindrical architecture typical of the post-implantation mouse embryo," the authors reported.
They further proposes that this stem cell model of mammalian embryogenesis might provide "a potentially powerful platform" to dissect physical and molecular
mechanisms that mediate the critical crosstalk during natural embryogenesis, and thus shed a little more light on the biology of pregnancy.
Some non-involved commentators thought the experiments made a stronger case for extending the 14-day limit on embryo research, while Robin Lovell-Badge of the Francis Crick Institute in London said the artificial embryos developed in Cambridge lacked two cell types (ectoderm and endoderm) required for functional development.
Commenting on behalf of ESHRE, Rita Vassena, a former co-ordinator of the SIG Stem Cells, said: "This is an exciting study which sheds light on the ability of stem cells to communicate and arrange themselves in coherent structures not unlike a developing embryo. This will be an incredible tool to study stages of development which have so far been inaccessible, and even provide in vitro models aimed at understanding normal development or the origin of certain diseases. But given the possible ethical implications in translating this work to the human, scientific research should be accompanied by public discussion and a clear regulatory framework.”
The co-ordinator of ESHRE’s SIG Stem Cells added: "Despite the fundamental and clinical significance of these results, study of the implantation period and the events governing post-implantation in the human remain exceptionally challenging. Studies are often not feasible and curbed by bioethical and legal concerns. So the promise of investigating certain embryonic milestones without the need for human embryos may shed light on previously unattainable stages of human development. In theory, such research may eventually contribute to both reproductive medicine, by improving pregnancy outcomes, and regenerative medicine, by enhancing and uncovering new stem cell differentiation protocols. However, it is important to note that caution should be taken when translating findings from artificial models to the in vivo human environment. Although we are one step closer, further studies are crucial for more direct human clinical applications.”
1. Harrison SE, Sozen B, Christodoulou N, et al. Assembly of embryonic and extra-embryonic stem cells to mimic embryogenesis in vitro; Science; 2 March 2017; DOI: 10.1126/science.aal1810