Great boost for research into early human development24 June 2021• PRESSRELEASE
Two research projects led by LUMC researchers have been granted a total of 7 million euros by ZonMw. Professor Niels Geijsen will, together with researchers from other institutes, create a model system that can be used to study the development of human organs. Professor Susana Chuva de Sousa Lopes aims to make sperm and egg cells from human stem cells. The projects will lead to a better understanding of human development and severe hereditary diseases.
"We do not fully understand how a human embryo develops yet," says Niels Geijsen, Professor of Developmental Biology and Regenerative Medicine. " A great deal of knowledge we have about this derives from studies with laboratory animals, but that knowledge cannot be translated directly to the human biology." "Due to ethical objections and practical problems, research on human embryos is only very limited," says Professor of Developmental Biology Susana Chuva de Sousa Lopes.
"That is why the government is asking for alternatives," says Chuva de Sousa Lopes. The ZonMw programme PSIDER, from which these projects were funded, is intended for this purpose. "The aim of this programme is to use human stem cells to make structures in the laboratory that serve as models for human embryonic development."
From stem cell to egg cell
Chuva de Sousa Lopes' project focuses on the so-called pre-implantation phase. "We will try to make egg cells and sperm cells from human stem cells," she says. This is expected to take up the entire duration of the project. "If this is successful, the next step would be to use these cells to create an embryo that is not viable but can be used for research," says Chuva de Sousa Lopes, "but we haven't got that far yet."
Development of an embryo
Niels Geijsen focuses on a later stage of development, just after implantation of the embryo. "With new embryo-like structures made from human stem cells, we hope to investigate how organs are formed," says Geijsen. These so-called gastruloids are model embryos that mimic the three-dimensional properties of embryos. Researchers can use them to study how an embryo develops a left and right side, and stomach and back with all organs in the right place. "The technique is still in its infancy, but it is very promising," says Geijsen.
Impact later in life
But why is it so important to understand early development? Geijsen: “These early stages are one of the most important moments in your life. Before a woman ealizes that she is pregnant, the first organs are already formed. If mistakes are made during this process, for example due to genetic defects, this can have serious consequences later in life.”
An example of such a condition is FSHD, a muscle disease that manifests from the age of ten. “The muscles in the face, shoulders and upper arms weaken, and this has a major impact on the quality of life of these patients. The question is why these muscles are affected, while other muscles, which have the same genetic error, are affected less or later.” As model embryos have the same 3D structure as a real embryo, this seems the perfect model to investigate why muscles in the head-shoulder area are affected and other muscles less so. "In a similar way, we want to investigate how genetic defects influence the development and function of the heart, and how mature blood cells are formed," says Geijsen.
Connection to society
Research with human embryos is always a sensitive subject, according to Chuva de Sousa Lopes. That is why a lot of room is built into these projects for the ethical and social aspects. "During our projects we will organise dialogue sessions in which everyone can participate. We want to involve the public to show what we do but also to hear what they think about it," says Chuva de Sousa Lopes.
The grants for Chuva de Sousa Lopes and Geijsen come from the ZonMw programme Pluripotent Stem Cells for Inherited Diseases and Embryonic Research (PSIDER). The awarded money is divided among the consortium partners. Chuva de Sousa Lopes' consortium consists of Amsterdam UMC, Erasmus MC, Maastricht University and Rathenau Institute. Geijsen works together with Erasmus MC, Hubrecht Institute, UMC Utrecht, Sanquin, Nemo Kennislink and UPF in Barcelona.