Scientists decode how pregnancies fail using stem cell models

LONDON: Scientists have created a stem cell-derived model of the human embryo in the lab by reprogramming human stem cells, a breakthrough which could help research into genetic disorders and in understanding why and how pregnancies fail.

This embryo model is an organised three-dimensional structure derived from pluripotent stem cells that replicate some developmental processes like origins of organs and specialised cells such as sperm and eggs, and facilitate understanding of early pregnancy loss, that occur in early human embryos.

The new models derived from human stem cells do not have a brain or beating heart, but they include cells that would typically go on to form the embryo, placenta and yolk sac, and develop to form the precursors of germ cells (that will form sperm and eggs).

Many pregnancies fail at the point when these three types of cells orchestrate implantation into the uterus begin to send mechanical and chemical signals to each other, which tell the embryo how to develop properly.

“Our human embryo-like model, created entirely from human stem cells, gives us access to the developing structure at a stage that is normally hidden from us due to the implantation of the tiny embryo into the mother’s womb,” said Professor Magdalena Zernicka-Goetz in the University of Cambridge’s Department of Physiology, Development and Neuroscience.

“This exciting development allows us to manipulate genes to understand their developmental roles in a model system. This will let us test the function of specific factors, which is difficult to do in the natural embryo,” she added, in the paper published in the journal Nature. In natural human development, the second week of development is an important time when the embryo implants into the uterus.

This is the time when many pregnancies are lost. The new advance enables scientists to peer into the mysterious ‘black box’ period of human development – usually following implantation of the embryo in the uterus – to observe processes never directly observed before.

Understanding these early developmental processes holds the potential to reveal some of the causes of human birth defects and diseases, and to develop tests for these in pregnant women. Until now, the processes could only be observed in animal models, using cells from zebrafish and mice, for example.