Following the 2017-2021 coalition agreement from the Rutte IV Cabinet in which it was recommended to focus on developing alternatives for research with human embryos, the Ministry of Health, Welfare and Sport commissioned ZonMw to implement a program for research with (human) induced pluripotent stem cells that can be used to (1) develop alternative model systems for human embryos, (2) advance our understanding of and ability to treat serious hereditary diseases, and (3) put the Netherlands at the forefront of this field.
The Pluripotent Stem cells for Inherited Diseases and Embryonic Research (PSIDER) program is intended for biomedical research with human induced pluripotent stem cells (hiPSCs). This program focuses on developing alternatives to human embryo research aimed at providing knowledge for the prevention and treatment of serious hereditary diseases.
Figure 1: Human development timeline and developmental period mimicked by different stem cell-derived embryo models.
The PSIDER research program is divided into two main research lines. Line 1 focuses on developing a broad range of hiPSC lines to create organoids that can provide (patient-specific) insights into the study of serious hereditary diseases. Line 2 focuses on developing and using hiPSC lines to create models capable of recapitulating the processes involved in gamete formation and early human development, and consists of three separate but interconnected consortia. The HipGametes consortium aims to use hiPSCs to develop egg and sperm cells that are genetically modified to preclude viability if used for fertilization, resulting in so-called ‘non-viable embryos’. The Beyond the Blastocyst consortium focuses on modeling the peri-implantation period of early human development with so-called ‘blastoids’. The GREAT consortium focuses on recapitulating processes associated with gastrulation, during which the embryo’s cells slowly differentiate into more specialized subtypes, with so-called ‘gastruloids’.
Read on about the PSIDER program here (in Dutch).
Understanding the intricate processes of gamete formation and early embryogenesis holds tremendous promise for advancing fundamental science and clinical applications. It could unlock critical insights into various human conditions and potentially lead to new therapeutic avenues. However, conducting this research has been historically challenging due to limited access to suitable research materials, compounded by technical, ethical, and legal considerations.
Recent breakthroughs have demonstrated that stem cells can emulate aspects of gamete formation and early embryo development under controlled laboratory conditions. Stem cells, obtained non-invasively and capable of robust expansion in culture, offer a unique opportunity to investigate human development from its earliest stages.
Their remarkable potential to differentiate into any cell type in the human body makes them highly adaptable tools for scientific inquiry.
Our consortia are focused on creating innovative models of human egg cells, sperm cells, and embryos using hiPSCs.
As part of PSIDER Line 2, each of our three consortia aims to harness the potential of hiPSCs to replicate certain aspects of human development in vitro. By doing so, we aim to deepen our understanding of gametogenesis and embryogenesis—critical periods where many human conditions arise—in a way that can meaningfully help refine, reduce, and replace the need for donated gametes and embryos as research material. Attention to ethical, legal, and social issues (ELSI), also known as Socially Responsible Innovation (MVI), is therefore a strong point of attention within each consortium.
Our multidisciplinary team of researchers aims to develop egg and sperm cells from (edited) hiPSCs in the laboratory, and to explore the ethical, legal, and societal implications of potentially using these cells (or: gametes) to create non-viable human embryos.
We use human blastoids to study the molecular mechanisms of early human development, develop methods to improve IVF success of mosaic embryos and develop an ethical framework that facilitates policy-making.
The GREAT consortium aims to develop a 3D human gastruloid model system from pluripotent stem cells. The aim is to study the early development of heart, muscle and blood tissue. At the same time, GREAT will explore the ethical and social issues of this technology.
Have questions about our research or interested in contributing to (one of) the consortia? Your input is invaluable to us and we’d love to hear from you. Feel free to reach out with any inquiries, ideas, or suggestions.
