Sato 2009: single Lgr5 stem cells build crypt-villus organoids
The experiment that invented organoids: a single intestinal stem cell, given three growth factors in a gel, grew into a miniature gut lining that could be kept alive indefinitely, a method since extended to tumours from individual patients.
Overview
Sato, Clevers and colleagues at the Hubrecht Institute showed that single Lgr5-positive stem cells from the mouse small intestine, embedded in Matrigel with EGF, Noggin and R-spondin 1 and no supporting mesenchyme, form self-organising structures with crypt and villus domains containing all the differentiated cell types of the gut. The organoids could be passaged for over eight months without losing their properties. The method was soon adapted to human tissue and to tumours, creating patient-derived organoids for drug testing.
- Single Lgr5-positive intestinal stem cells formed crypt-villus organoids in Matrigel with EGF, Noggin and R-spondin 1, without a mesenchymal niche.
- Organoids contained all differentiated intestinal cell types and could be maintained for more than eight months.
- The defined culture conditions were the basis for later human and tumour organoid systems.
Organoids from patients' tumours are now used to test drugs before treatment, to model rare cancers and to study resistance. Every one of those systems descends from this culture method.
- Mouse intestine only in this paper; human and tumour organoids came in later work.
- Organoids lack blood vessels, immune cells and stroma unless these are added.
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