Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease
Abstract Identification of tissue‐specific renal stem/progenitor cells with nephrogenic potential is a critical step in developing cell‐based therapies for renal disease. In the human kidney, stem/progenitor cells are induced into the nephrogenic pathway to form nephrons until the 34 week of gestati...
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| Format: | Article |
| Language: | English |
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Springer Nature
2013-09-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.1002/emmm.201201584 |
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| author | Orit Harari‐Steinberg Sally Metsuyanim Dorit Omer Yehudit Gnatek Rotem Gershon Sara Pri‐Chen Derya D. Ozdemir Yaniv Lerenthal Tzahi Noiman Herzel Ben‐Hur Zvi Vaknin David F. Schneider Bruce J. Aronow Ronald S. Goldstein Peter Hohenstein Benjamin Dekel |
| author_facet | Orit Harari‐Steinberg Sally Metsuyanim Dorit Omer Yehudit Gnatek Rotem Gershon Sara Pri‐Chen Derya D. Ozdemir Yaniv Lerenthal Tzahi Noiman Herzel Ben‐Hur Zvi Vaknin David F. Schneider Bruce J. Aronow Ronald S. Goldstein Peter Hohenstein Benjamin Dekel |
| author_sort | Orit Harari‐Steinberg |
| collection | DOAJ |
| description | Abstract Identification of tissue‐specific renal stem/progenitor cells with nephrogenic potential is a critical step in developing cell‐based therapies for renal disease. In the human kidney, stem/progenitor cells are induced into the nephrogenic pathway to form nephrons until the 34 week of gestation, and no equivalent cell types can be traced in the adult kidney. Human nephron progenitor cells (hNPCs) have yet to be isolated. Here we show that growth of human foetal kidneys in serum‐free defined conditions and prospective isolation of NCAM1+ cells selects for nephron lineage that includes the SIX2‐positive cap mesenchyme cells identifying a mitotically active population with in vitro clonogenic and stem/progenitor properties. After transplantation in the chick embryo, these cells—but not differentiated counterparts—efficiently formed various nephron tubule types. hNPCs engrafted and integrated in diseased murine kidneys and treatment of renal failure in the 5/6 nephrectomy kidney injury model had beneficial effects on renal function halting disease progression. These findings constitute the first definition of an intrinsic nephron precursor population, with major potential for cell‐based therapeutic strategies and modelling of kidney disease. |
| format | Article |
| id | doaj-art-b0a80b1c58cc4d72bc2064b920df87ed |
| institution | OA Journals |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2013-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-b0a80b1c58cc4d72bc2064b920df87ed2025-08-20T02:11:29ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842013-09-015101556156810.1002/emmm.201201584Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal diseaseOrit Harari‐Steinberg0Sally Metsuyanim1Dorit Omer2Yehudit Gnatek3Rotem Gershon4Sara Pri‐Chen5Derya D. Ozdemir6Yaniv Lerenthal7Tzahi Noiman8Herzel Ben‐Hur9Zvi Vaknin10David F. Schneider11Bruce J. Aronow12Ronald S. Goldstein13Peter Hohenstein14Benjamin Dekel15The Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical CenterThe Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical CenterThe Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical CenterThe Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical CenterThe Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical CenterThe Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical CenterThe Roslin Institute, University of Edinburgh, Easter Bush CampusCancer Research Center, Sheba Medical CenterMina and Everard Goodman Faculty of Life Sciences, Bar‐IlanUniversityL.E.M. Laboratory of Early DetectionDepartment of Obstet and Gynecology, Assaf HarofehDepartment of Obstet and Gynecology, Assaf HarofehDivision of Molecular and Developmental Biology, Department of Pediatrics, University of Cincinnati, Childrens Hospital Medical CenterMina and Everard Goodman Faculty of Life Sciences, Bar‐IlanUniversityThe Roslin Institute, University of Edinburgh, Easter Bush CampusThe Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical CenterAbstract Identification of tissue‐specific renal stem/progenitor cells with nephrogenic potential is a critical step in developing cell‐based therapies for renal disease. In the human kidney, stem/progenitor cells are induced into the nephrogenic pathway to form nephrons until the 34 week of gestation, and no equivalent cell types can be traced in the adult kidney. Human nephron progenitor cells (hNPCs) have yet to be isolated. Here we show that growth of human foetal kidneys in serum‐free defined conditions and prospective isolation of NCAM1+ cells selects for nephron lineage that includes the SIX2‐positive cap mesenchyme cells identifying a mitotically active population with in vitro clonogenic and stem/progenitor properties. After transplantation in the chick embryo, these cells—but not differentiated counterparts—efficiently formed various nephron tubule types. hNPCs engrafted and integrated in diseased murine kidneys and treatment of renal failure in the 5/6 nephrectomy kidney injury model had beneficial effects on renal function halting disease progression. These findings constitute the first definition of an intrinsic nephron precursor population, with major potential for cell‐based therapeutic strategies and modelling of kidney disease.https://doi.org/10.1002/emmm.201201584developmentkidney stem cellsprogenitor cellsregenerationstem cells |
| spellingShingle | Orit Harari‐Steinberg Sally Metsuyanim Dorit Omer Yehudit Gnatek Rotem Gershon Sara Pri‐Chen Derya D. Ozdemir Yaniv Lerenthal Tzahi Noiman Herzel Ben‐Hur Zvi Vaknin David F. Schneider Bruce J. Aronow Ronald S. Goldstein Peter Hohenstein Benjamin Dekel Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease EMBO Molecular Medicine development kidney stem cells progenitor cells regeneration stem cells |
| title | Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease |
| title_full | Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease |
| title_fullStr | Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease |
| title_full_unstemmed | Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease |
| title_short | Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease |
| title_sort | identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease |
| topic | development kidney stem cells progenitor cells regeneration stem cells |
| url | https://doi.org/10.1002/emmm.201201584 |
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