Adult human CD133/1+ kidney cells isolated from papilla integrate into developing kidney tubules

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1812

Article

Ward, Heather H.^1,2,3  Romero, Elsa¹  Welford, Angela¹  Pickett, Gavin⁴  Bacallao, Robert^2,3  Gattone, Vincent H., II⁵  Ness, Scott A.^4,6  Wandinger-Ness, Angela^1,4  Roitbak, Tamara⁷ 

[1] Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Albuquerque, NM 87131 USA

[2] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA

[3] Indiana Univ, Sch Med, Div Nephrol, Indianapolis, IN 46202 USA

[4] Univ New Mexico, Hlth Sci Ctr, Ctr Canc, Albuquerque, NM 87131 USA

[5] Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA

[6] Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA

[7] Univ New Mexico, Hlth Sci Ctr, Dept Neurosurg, Albuquerque, NM 87131 USA

关键词: Kidney disease;    ADPKD;    Regenerative medicine;    Renopoietic;    Mesenchymal stem cell;    Tamm-Horsfall/uromodulin;    Metanephric organ culture;    Xanthosine;   

DOI  :  10.1016/j.bbadis.2011.01.010

来源: Elsevier

【 摘 要 】

Approximately 60,000 patients in the United States are waiting for a kidney transplant due to genetic, immunologic and environmentally caused kidney failure. Adult human renal stem cells could offer opportunities for autologous transplant and repair of damaged organs. Current data suggest that there are multiple progenitor types in the kidney with distinct localizations. In the present study, we characterize cells derived from human kidney papilla and show their capacity for tubulogenesis. In situ, nestle and CD133/1(+) cells were found extensively intercalated between tubular epithelia in the loops of Henle of renal papilla, but not of the cortex. Populations of primary cells from the renal cortex and renal papilla were isolated by enzymatic digestion from human kidneys unsuited for transplant and immuno-enriched for CD133/1(+) cells. Isolated CD133/1(+) papillary cells were positive for nestin, as well as several human embryonic stem cell markers (SSEA4, Nanog, SOX2, and OCT4/POU5F1) and could be triggered to adopt tubular epithelial and neuronal-like phenotypes. Isolated papillary cells exhibited morphologic plasticity upon modulation of culture conditions and inhibition of asymmetric cell division. Labeled papillary cells readily associated with cortical tubular epithelia in co-culture and 3-dimensional collagen gel cultures. Heterologous organ culture demonstrated that CD133/1(+) progenitors from the papilla and cortex became integrated into developing kidney tubules. Tubular epithelia did not participate in tubulogenesis. Human renal papilla harbor cells with the hallmarks of adult kidney stem/progenitor cells that can be amplified and phenotypically modulated in culture while retaining the capacity to form new kidney tubules. This article is part of a Special Issue entitled: Polycystic Kidney Disease. (C) 2011 Elsevier B.V. All rights reserved.

【 授权许可】

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