Written by event reporter Elisa Heinzelmann

The ability to grow human tissues from stem cells in 3D culture has the potential to revolutionize drug discovery processes and regenerative medicine. Building on a long tradition of cell and developmental biology knowledge, organoids resembling a variety of human tissues have already been generated today. These 3D structures offer an opportunity to explore the complexities of human biology.

This year’s EMBO | EMBL Organoid Symposium again brought together the leading researchers in this field, uniting their collective expertise to strengthen a new research community and reveal new insights into various tissue models. The aim of this meeting was to bring together researchers from different angles of the organoid field to enhance our understanding of how organoids can be formed and maintained, how they can be used to study disease and how we might eventually use them to regenerate and replace human organ tissue. And, without revealing too much at this point, I can say it was a success.

 

My journey began with the opening remarks by Esther Schnapp, Senior Editor at EMBO, who was setting the stage for a comprehensive exploration of organoid research. The question she posed, “Where do we stand with Organoid research?”, opened the exciting journey across 5 sessions, joined by 466 on-site participants and 280 virtual attendees:

Session 1: Concepts from Development and Evolution

In the past, the study of human development has largely been limited to observational studies on preimplantation embryos or progenitor cells and tissue isolated from aborted fetuses. However, the advent of a variety of organoid models derived from iPSCs has provided a path toward dynamic observation and mechanistic studies of human development. A basic approach to study human development are organoid models derived from iPSC. First, organ-specific progenitors are generated from iPSCs by passing them through a sequence of exposures to defined factors. After further culture, the progenitors self-organize into organoids representative of the developing organ. This approach provides insight into the morphogenesis of several organ systems, and more intriguingly, is beginning to shed light on how human genetics impact developmental diseases of the brain, lung, and gut.

Gray Camp’s presentation, “Charting Human Development with Organoid Single-Cell Technologies.” Camp, from the Institute of Human Biology and Roche Pharma Research and Development, Switzerland, unveiled the creation of atlases that provide a single-cell resolution of developing and adult human organs and their organoid counterparts. These atlases are instrumental in shedding light on cell states, tracking differentiation pathways, and identifying organ-specific interactions. Furthermore, they serve as valuable benchmarks for stem cell-derived organoids, aiding researchers in comprehending the molecular and cellular dynamics of organ development, disease, and evolution.

Exploring #EESOrgan: A visual journey capturing the unique symposium venue at EMBL in Heidelberg, enlightening presentations, amazing catering, and lively parties.

Session 2: Building Complex Organoids

This session delved into the art of constructing complex organoids. Talks such as “Self-organization in Pancreas Organoids: Formation of Complex Ductal Networks” and “Complex Intestinal Organoid Models to Study Immune-Epithelial Interactions” ignited fervent discussions. The focal point here was complexity and improvement. Researchers are ardently working to enhance the organoid model, incorporating elements like immune cells, neurons, the extracellular matrix, and even bacteria.

The generation of more complex organoid models from divers starting cell populations also brings new challenges to the field. Madeline Lancaster, from the MRC Laboratory of Molecular Biology in the United Kingdom, presented why certain cell lines excel in generating brain organoids while others do not. This inquiry has unveiled a specific epigenetic footprint associated with suboptimal cell lines, a discovery that can be reversed using a cocktail of small molecules. This groundbreaking technique not only promises more reliable disease modeling and therapeutic discovery but also unravels the earliest mysteries of pluripotent stem cell fate determination.

Session 3: Organoids from Adult Stem Cells

Adult stem cell organoids are composed of an epithelial monolayer that mimics the 3D architecture and contains the cell types of the desired organ to be modelled. The work on these adult stem cell organoids was pioneered by Hans Clevers, who generated the first mouse intestinal organoid cultures. In his talk, Clevers elucidated the significance of Lgr5+ crypt base columnar cells as the cornerstone of the small intestine and colon, emphasizing their role in generating diverse epithelial lineages. The manipulation of genes within these organoids via CRISPR/Cas9 technology promises a new era in personalized medicine and even the potential to replace donor organs.

Over the last years, the number adult stem cell organoids of from diverse tissues and organs is growing. The session showcased that they have been generated from almost all endoderm-derived tissues, such as colon, liver, pancreas, and lung.     

Session 4: Organoids in Regenerative Medicine/Therapy

This session focused on the therapeutic potential of organoids. The talk of Karl Koehler, one of the Symposium’s organizer and group leader at the Boston Children’s Hospital, embarked on “Skin Organoids for Developmental Modeling and Cell Therapy”. Koehler’s insights revolved around the challenge of recreating the complex structure of skin in organoid cultures. He shared his latest advances in controlling the co-development of epidermal and dermal progenitor cells, all starting from human pluripotent stem cells. This groundbreaking work triggers the self-assembly of full-thickness skin organoids, complete with hair follicles and sensory nerves.

This visionary research by Koehler as well as by other speakers of the session illustrates the enormous potential of organoids not only for unraveling disease etiology but also for advancing groundbreaking therapies. The power of organoids is not confined to understanding health and disease – it extends into the realm of healing and recovery.

Session 5: Organoids in Disease Modeling

The symposium’s final session delved deep into how organoids help us understand diseases better. From deciphering the virulence strategies of enterobacterial pathogens to achieve efficient colonization of the human intestinal epithelium (by Petra Geiser, Uppsala University, Sweden) to pinpointing the use of liver organoids to study regeneration and cancer (by Meritxell Huch, Max Planck Institute of Molecular Cell Biology and Genetics, Germany) these talks spanned a broad spectrum of human diseases.

The session closed with a keynote lecture given by Juergen Knoblich (Institute of Molecular Biotechnology, Austria). He offered an insight into the potential of cerebral organoids to understand complex brain disorders, their origins, and possible treatments. Knoblich’s lecture was not just informative; it was a profound exploration of the future of neuroscience, where organoids play a pivotal role in advancing our understanding of the most intricate organ in the human body.