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

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, nestin+ 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.

Graphical AbstractHuman CD133/1+ and nestin+ cells intercalated in tubules deep within the kidney papilla exhibit morphologic plasticity and the capacity to undergo tubulogenesis in vitro. (1) Lectin-stained, developing kidney tubules in metanephric organ culture. (2) CD133/1+ and nestin+ cells intercalated in Tamm–Horsfall labeled loops of Henle. (3) CD133/1+ cells form spheroids in culture. (4) Cortical Tamm–Horsfall labeled loops of Henle are devoid of dually CD133/1+ and nestin+ cells. (5) Isolated CD133/1+ papillary cell stained for actin and nestin.Figure optionsDownload high-quality image (275 K)Download as PowerPoint slideResearch Highlights
► Human CD133/1+ and nestin+ cells are intercalated in loop of Henle tubules deep within the kidney papilla.
► Isolated CD133/1+ and nestin+ cells express embryonic stem cell marker SSEA4 and exhibit morphologic plasticity in vitro.
► Human renal progenitors undergo tubulogenesis in metanephric organ culture.
► Heterologous metanephric organ culture can be used to identify and characterize adult human stem cells.