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2015 ; 6
(ä): 239
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Progenitor-like cells derived from mouse kidney protect against renal fibrosis in
a remnant kidney model via decreased endothelial mesenchymal transition
#MMPMID26631265
Chen CL
; Chou KJ
; Fang HC
; Hsu CY
; Huang WC
; Huang CW
; Huang CK
; Chen HY
; Lee PT
Stem Cell Res Ther
2015[Dec]; 6
(ä): 239
PMID26631265
show ga
INTRODUCTION: Pathophysiological changes associated with chronic kidney disease
impair angiogenic processes and increase renal fibrosis. Progenitor-like cells
derived from adult kidney have been previously used to promote regeneration in
acute kidney injury, even though it remained unclear whether the cells could be
beneficial in chronic kidney disease (CKD). METHODS: In this study, we
established a CKD model by five-sixths nephrectomy and mouse kidney
progenitor-like cells (MKPCs) were intravenously administered weekly for 5 weeks
after establishing CKD. We examined the impact of MKPCs on the progression of
renal fibrosis and the potential of MKPCs to preserve the angiogenic process and
prevent endothelial mesenchymal transition in vivo and in vitro. RESULTS: Our
results demonstrate that the MKPCs delayed interstitial fibrosis and the
progression of glomerular sclerosis and ameliorated the decline of kidney
function. At 17 weeks, the treated mice exhibited lower blood pressures, higher
hematocrit levels, and larger kidney sizes than the control mice. In addition,
the MKPC treatment prolonged the survival of the mice with chronic kidney
injuries. We observed a decreased recruitment of macrophages and myofibroblasts
in the interstitium and the increased tubular proliferation. Notably, MKPC both
decreased the level of vascular rarefaction and prevented endothelial mesenchymal
transition (EndoMT) in the remnant kidneys. Moreover, the conditioned medium from
the MKPCs ameliorated endothelial cell death under hypoxic culture conditions and
prevented TGF-?-induced EndoMT through downregulation of phosphorylated Smad 3 in
vitro. CONCLUSIONS: MKPCs may be a beneficial treatment for kidney diseases
characterized by progressive renal fibrosis. The enhanced preservation of
angiogenic processes following MKPC injections may be associated with decreased
fibrosis in the remnant kidney. These findings provide further understanding of
the mechanisms involved in these processes and will help develop new cell-based
therapeutic strategies for regenerative medicine in renal fibrosis.