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2016 ; 7
(1
): 68
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The role of long-term label-retaining cells in the regeneration of adult mouse
kidney after ischemia/reperfusion injury
#MMPMID27137761
Liu X
; Liu H
; Sun L
; Chen Z
; Nie H
; Sun A
; Liu G
; Guan G
Stem Cell Res Ther
2016[Apr]; 7
(1
): 68
PMID27137761
show ga
BACKGROUND: Label-retaining cells (LRCs) have been recognized as rare stem and
progenitor-like cells, but their complex biological features in renal repair at
the cellular level have never been reported. This study was conducted to evaluate
whether LRCs in kidney are indeed renal stem/progenitor cells and to delineate
their potential role in kidney regeneration. METHODS: We utilized a long-term
pulse chase of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells in C57BL/6J mice to
identify renal LRCs. We tracked the precise morphological characteristics and
locations of BrdU(+)LRCs by both immunohistochemistry and immunofluorescence. To
examine whether these BrdU(+)LRCs contribute to the repair of acute kidney
injury, we analyzed biological characteristics of BrdU(+)LRCs in mice after
ischemia/reperfusion (I/R) injury. RESULTS: The findings revealed that the nuclei
of BrdU(+) LRCs exhibited different morphological characteristics in normal adult
kidneys, including nuclei in pairs or scattered, fragmented or intact, strongly
or weakly positive. Only 24.3 ± 1.5 % of BrdU(+) LRCs co-expressed with Ki67 and
9.1 ± 1.4 % of BrdU(+) LRCs were positive for TUNEL following renal I/R injury.
Interestingly, we found that newly regenerated cells formed a niche-like
structure and LRCs in pairs tended to locate in this structure, but the number of
those LRCs was very low. We found a few scattered LRCs co-expressed Lotus
tetragonolobus agglutinin (LTA) in the early phase of injury, suggesting
differentiation of those LRCs in mouse kidney. CONCLUSIONS: Our findings suggest
that LRCs are not a simple type of slow-cycling cells in adult kidneys,
indicating a limited role of these cells in the regeneration of I/R injured
kidney. Thus, LRCs cannot reliably be considered stem/progenitor cells in the
regeneration of adult mouse kidney. When researchers use this technique to study
the cellular basis of renal repair, these complex features of renal LRCs and the
purity of real stem cells among renal LRCs should be considered.