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Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney.
- Source :
-
Nature cell biology [Nat Cell Biol] 2014 Jan; Vol. 16 (1), pp. 118-26. Date of Electronic Publication: 2013 Dec 15. - Publication Year :
- 2014
-
Abstract
- With the prevalence of end-stage renal disease rising 8% per annum globally, there is an urgent need for renal regenerative strategies. The kidney is a mesodermal organ that differentiates from the intermediate mesoderm (IM) through the formation of a ureteric bud (UB) and the interaction between this bud and the adjacent IM-derived metanephric mesenchyme (MM). The nephrons arise from a nephron progenitor population derived from the MM (ref. ). The IM itself is derived from the posterior primitive streak. Although the developmental origin of the kidney is well understood, nephron formation in the human kidney is completed before birth. Hence, there is no postnatal stem cell able to replace lost nephrons. In this study, we have successfully directed the differentiation of human embryonic stem cells (hESCs) through posterior primitive streak and IM under fully chemically defined monolayer culture conditions using growth factors used during normal embryogenesis. This differentiation protocol results in the synchronous induction of UB and MM that forms a self-organizing structure, including nephron formation, in vitro. Such hESC-derived components show broad renal potential ex vivo, illustrating the potential for pluripotent-stem-cell-based renal regeneration.
- Subjects :
- Animals
Blastocyst Inner Cell Mass cytology
Cell Aggregation
Cell Culture Techniques
Fibroblast Growth Factor 9 metabolism
Humans
Mesoderm cytology
Mice
Nephrons cytology
Nephrons embryology
Primitive Streak cytology
Time Factors
Ureter cytology
Ureter embryology
Cell Differentiation
Cell Lineage
Embryonic Stem Cells cytology
Kidney cytology
Kidney embryology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4679
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 24335651
- Full Text :
- https://doi.org/10.1038/ncb2894