title: "Miniguts" from plucked human hair meet Crohn's disease.
abstract: Human pluripotent stem cells represent a powerful tool to study human embryonic development and disease but also open up novel strategies for cell replacement therapies. Their capacity to give rise to every cell type of the human body, meanwhile, enables researchers to generate high yields of mesodermal, ectodermal, but also endodermal-derived tissues such as hepatic, pancreatic, or intestinal cells. Another progress in the field came with the advent of 3-dimensional culture conditions, so-called organoids, which facilitate maturation of stem cells and in turn more faithfully recapitulate human tissue architecture. While several studies reported the derivation of organoid cultures from adult intestinal tissue, the derivation of intestinal organoids derived from plucked human hair of Crohn's disease patients has not been reported. The current research project reports such successful generation and characterization of induced pluripotent stem cells (iPSCs) derived from hair sheet keratinocyte cultures of a patient with Crohn's disease. Stepwise differentiation along the intestinal lineage showed no differences in intermediate stages such as definitive endoderm formation. We also directed the patterned primitive gut tube toward intestinal organoids resembling the cellular architecture of human "miniguts". As expected from current pathophysiological knowledge on Crohn's disease, there were no obvious morphological differences in the "miniguts" derived from healthy control and diseased patient-induced pluripotent stem cells. Taken together, our platform will enable for detailed and complementary phenotyping of the pathophysiology of Crohn's disease in a novel disease-in-a-dish format.
authors.forename: M
authors.initials: M
authors.lastname: Hohwieler
authors.forename: S
authors.initials: S
authors.lastname: Renz
authors.affiliation: Institute of Neuroanatomy, Eberhard Karls University Tuebingen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Liebau
authors.affiliation: Department of Cell Biology, Institute for Biomedical Engineering, Medical Faculty, RWTH University Aachen, Germany.
authors.forename: Q
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine I, Ulm University, Ulm, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Lechel
authors.affiliation: Department of Internal Medicine I, Ulm University, Ulm, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Klaus
authors.affiliation: Department of Internal Medicine I, Ulm University, Ulm, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Perkhofer
authors.affiliation: Department of Cell Biology, Institute for Biomedical Engineering, Medical Faculty, RWTH University Aachen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zenke
authors.affiliation: Department of Internal Medicine I, Ulm University, Ulm, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Seufferlein
authors.affiliation: Department of Internal Medicine I, Ulm University, Ulm, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Illing
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: A
authors.initials: A
authors.lastname: Kleger
mesh_terms: D002454:Cell Differentiation; D003424:Crohn Disease / Q000473:pathology*; D006197:Hair / Q000473:pathology*; D006204:Hair Removal; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000473:pathology*; D007422:Intestines / Q000254:growth & development* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods