Hans Clevers is a renowned Dutch molecular geneticist and stem cell researcher whose work has profoundly influenced modern biology and medicine. He is recognized for identifying and characterizing adult stem cells, and for developing organoid technology, which creates miniature, self-organizing organ structures in the laboratory.
Identifying Adult Stem Cells
Hans Clevers’ research began with an investigation into adult stem cells, particularly those in the intestine. His group identified a specific marker, Lgr5 (Leucine-rich repeat-containing G-protein coupled receptor 5), expressed in cycling columnar cells at the base of intestinal crypts. These Lgr5-positive cells were shown to generate all epithelial lineages within the small intestine and colon over an extended period, confirming their role as adult stem cells.
The discovery of Lgr5 as a universal marker for adult stem cell populations was a significant advancement. Clevers and his team further demonstrated that Lgr5 also marks stem cells in other tissues, including the stomach and hair follicles. This finding shifted the scientific understanding of tissue regeneration, highlighting the broad potential of adult stem cells beyond previously emphasized embryonic stem cells. This research provided foundational knowledge about how tissues maintain themselves and repair damage throughout an organism’s life.
Developing Organoid Technology
Building upon the identification of Lgr5-positive stem cells, Clevers’ team developed organoid technology. Organoids are miniature, self-organizing three-dimensional structures grown from stem cells that closely mimic the architecture and function of actual organs. These “mini-organs” can be grown in vitro (outside the body) in a laboratory.
The process involves culturing adult stem cells, often Lgr5-positive cells, from tissues in a specialized gel, such as a “bio gel,” that provides structural support and simulates the natural environment. Over approximately ten days, these stem cells divide and self-organize into structures that recapitulate many characteristics of the original tissue, including cell type diversity. This technology has transformed the ability to study human biology and disease in a controlled environment, offering a new model system that bridges the gap between traditional two-dimensional cell cultures and complex animal models.
Implications for Disease and Medicine
The development of organoid technology has applications across medicine and disease research. Organoids provide a more accurate and physiologically relevant model than conventional 2D cell cultures or animal models for studying human biology. For instance, they have been used to model human diseases like cystic fibrosis and colorectal cancer, offering insights into disease progression and mechanisms.
Organoids are valuable for drug testing, allowing researchers to screen new drugs and assess their effectiveness and toxicity in a human-relevant system. This capability can reduce reliance on animal testing and potentially accelerate the drug discovery process. Organoids are also explored for understanding infectious diseases, such as SARS-CoV-2 infection, and hold promise for developing regenerative therapies, including growing genetically matched donor organs for transplantation.
Ongoing Contributions to Science
Hans Clevers continues to be a prominent figure in science, with ongoing influence and leadership. He previously served as the President of the Royal Netherlands Academy of Arts and Sciences and is currently the Head of Pharma Research and Early Development (pRED) at Roche, a Swiss healthcare company. In this role, he oversees early research and discovery, including the establishment of the Institute of Human Biology, aiming to connect academic and pharmaceutical research.
His current research continues to focus on using adult stem cell-derived organoids to investigate the molecular mechanisms of tissue development and cancer. Clevers’ legacy is marked by his contributions to stem cell biology and his role in establishing organoid technology as a tool, shaping the future of biomedical research and personalized medicine.