title: Development of embryonic stem cells in recombinant kidneys.
abstract: Embryonic stem cells (ESC) are self-renewing and can generate all cell types during normal development. Previous studies have begun to explore fates of ESCs and their mesodermal derivatives after injection into explanted intact metanephric kidneys and neonatal kidneys maturing in vivo. Here, we exploited a recently described recombinant organ culture model, mixing fluorescent quantum dot labeled mouse exogenous cells with host metanephric cells. We compared abilities of undifferentiated ESCs with ESC-derived mesodermal or non-mesodermal cells to contribute to tissue compartments within recombinant, chimeric metanephroi. ESC-derived mesodermal cells downregulated Oct4, a marker of undifferentiated cells, and, as assessed by locations of quantum dots, contributed to Wilms' tumor 1-expressing forming nephrons, synaptopodin-expressing glomeruli, and organic ion-transporting tubular epithelia. Similar results were observed when labeled native metanephric cells were recombined with host cells. In striking contrast, non-mesodermal ESC-derived cells strongly inhibited growth of embryonic kidneys, while undifferentiated ESCs predominantly formed Oct4 expressing colonies between forming nephrons and glomeruli. These findings clarify the conclusion that ESC-derived mesodermal cells have functional nephrogenic potential, supporting the idea that they could potentially replace damaged epithelia in diseased kidneys. On the other hand, undifferentiated ESCs and non-mesodermal precursors derived from ESCs would appear to be less suitable materials for use in kidney cell therapies.
authors.affiliation: Institute of Translational Medicine; the University of Liverpool; Liverpool, UK.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Rak-Raszewska
authors.forename: Bettina
authors.initials: B
authors.lastname: Wilm
authors.forename: David
authors.initials: D
authors.lastname: Edgar
authors.forename: Simon
authors.initials: S
authors.lastname: Kenny
authors.forename: Adrian S
authors.initials: AS
authors.lastname: Woolf
authors.forename: Patricia
authors.initials: P
authors.lastname: Murray
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002678:Chimera; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007668:Kidney / Q000166:cytology*; D007684:Kidney Tubules / Q000166:cytology; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D009924:Organ Culture Techniques / Q000379:methods*; D009928:Organ Specificity; D045663:Quantum Dots
chemical_list: D015415:Biomarkers; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D049452:Green Fluorescent Proteins
keywords: differentiation; embryonic stem cell; kidney; mesoderm; metanephros; nephrogenesis; organic anion transport; quantum dot; rudiment