Final Report Summary - STEMCELLMARK (LGR receptors mark adult stem cells in multiple mammalian tissues)
The project was aimed at identifying stem cells of multiple internal organs using the Lgr5 marker previously characterized in our lab, as well as its family members. Subsequently, these cells were to be characterized functionally and molecularly. The mouse models used would then be validated by the discovery of the same cells in human organs as well as human tumors.
The project has been an overwhelming success. We have identified a number of novel stem cells including those of the stomach, the liver, the pancreas and the sebaceous glands. Furthermore, the project proposed several ‘high-risk, high-gain’ aims, all involving the establishment of a technology that allows for the in vitro expansion if these stem cells, against the dogma that non-transformed cells can not be propagated in culture without transformation. It is now possible to culture stem cells from a series of mouse and human organs into mini-versions of these organs, without inducing genetic or phenotypic changes. This has already allowed transplantation of the offspring of a single stem cell from colon or from liver into multiple recipient mice. Organoids can be grown from healthy tissue, but also from cancers or from genetically challenged organs, such as in Cystic Fibrosis patients.
The technology is currently implemented through the generation of large biobanks consisting of cultures of patient-specific disease samples such as tumor organoids or organoids from cystic fibrosis patients. The biobank platform allows us for the first time to test patient-specific samples for their response to conventional or new therapies. The stem cells identified in this project and the methods to expand them indefinitely in vitro holds great promise for the study of basic aspects of adult stem cell biology, for patient-specific drug development platforms,. The technology also offers a novel genetically stable source of cells for regenerative and/or gene therapy.
The project has been an overwhelming success. We have identified a number of novel stem cells including those of the stomach, the liver, the pancreas and the sebaceous glands. Furthermore, the project proposed several ‘high-risk, high-gain’ aims, all involving the establishment of a technology that allows for the in vitro expansion if these stem cells, against the dogma that non-transformed cells can not be propagated in culture without transformation. It is now possible to culture stem cells from a series of mouse and human organs into mini-versions of these organs, without inducing genetic or phenotypic changes. This has already allowed transplantation of the offspring of a single stem cell from colon or from liver into multiple recipient mice. Organoids can be grown from healthy tissue, but also from cancers or from genetically challenged organs, such as in Cystic Fibrosis patients.
The technology is currently implemented through the generation of large biobanks consisting of cultures of patient-specific disease samples such as tumor organoids or organoids from cystic fibrosis patients. The biobank platform allows us for the first time to test patient-specific samples for their response to conventional or new therapies. The stem cells identified in this project and the methods to expand them indefinitely in vitro holds great promise for the study of basic aspects of adult stem cell biology, for patient-specific drug development platforms,. The technology also offers a novel genetically stable source of cells for regenerative and/or gene therapy.