The renal papilla is a niche for adult kidney stem cells
J. Clin. Invest. Juan A. Oliver, et al. 114:795 doi:10.1172/JCI20921 [
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Figure 4Renal papillary cells grown in cell culture. (
A) Isolated renal papillary cells grown in standard cell culture conditions formed cell aggregates within about 24 hours of their isolation and expressed ZO-1 in their tight junctions. (
B and
C) Phase-contrast (Phase;
B) and fluorescence (
C) microphotographs of a group of renal papillary cells growing in cell culture conditions 4 days after cell isolation; about 40% of the papillary cells isolated from BrdU-loaded animals were BrdU-retaining cells. (
D and
E) During the first several days of culture, most cells had an epithelial phenotype expressing ZO-1 in their tight junctions (
D), but some cells, in addition to ZO-1, also expressed mesenchymal proteins such as α-smooth muscle actin (αSMA) (
E). (
F) After more than a week in culture under control conditions with 5% CO
2 and 95% room air, most cells were spindle-shaped and stained strongly for α-smooth muscle actin. (
G) However, when cells were grown under hypoxic conditions (5% CO
2, 1.5% O
2, and 93.5% N
2), most cells retained an epithelial phenotype, with prominent ZO-1 expression. (
H) When grown in standard control cell culture media on plastic, most cells adhered to the culture dish but frequently formed cell aggregates that resembled neurospheres. (
I) The tendency for the cells to aggregate was markedly enhanced by growth of the cells in the absence of sera. The picture shows a 3-week-old culture with many cellular aggregates. (
J) Many of the cells inside the aggregates were positive for nestin. Scale bars: 50 μm.