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

Abstract

Approximately 60,000 patients in the US 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.

Myocardial Self-Repair and Congenital Heart Disease

“…The neonatal human heart is a rich source of CPC bearing markers such as SSEA4, Isl1, Nkx2.5, and c-Kit. In addition to our report of myocardial SSEA4 localization (Amir et al, 2008), SSEA4 expression has been previously only reported in adult human kidney (Ward et al, 2011). Isl1 + CPC have also been localized to the atrium (Laugwitz et al, 2005).…”

Collecting Duct-Derived Cells Display Mesenchymal Stem Cell Properties and Retain Selective In Vitro and In Vivo Epithelial Capacity

“…The human renal papilla has also been reported to contain epithelial Oct4-expressing prominin/CD133 + cells in loops of Henle that form epithelial structures in vitro. 48,49 Our kidney MSClike cells are derived from collecting duct and home specifically back to that tubular segment, suggesting no overlap with these studies.…”

Dual-Purpose Bioreactors to Monitor Noninvasive Physical and Biochemical Markers of Kidney and Liver Scaffold Recellularization

“…35-010-CV, Corning) and 1% penicillin/streptomycin. Bioreactors were transferred to an incubator and perfused at 5 mL/min for at least 1 h. For seeding, perfusion was halted, and 40 million immortalized Madin-Darby canine kidney (MDCK) cells 21,22 or 6.25 million primary human renal papillae-derived CD133/1 + cells from anonymous cadaveric donors 23 were loaded into a syringe (2 mL volume) and manually injected at *2 mL/min…”

“…Placing this finding in context of other methods of cell delivery into the scaffold, this method of tubular repopulation is more efficient compared to infusion of cells through the ureter or artery at flow rates (e.g., <1 mL/min) which others have shown to preferentially restrict cells to glomeruli and nearby arterioles. 7,10,15,16 We additionally infused primary CD133/1 + human renal progenitor cells recovered from the renal papillae 23 using the arterial seeding method to validate the bioreactor system using primary cells. We observed similar dispersion of the cells throughout the renal cortex over a 3-and 7-day culture period (Fig.…”