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Influence of erythropoietin on microvesicles derived from mesenchymal stem cells
protecting renal function of chronic kidney disease
#MMPMID25998259
Wang Y
; Lu X
; He J
; Zhao W
Stem Cell Res Ther
2015[May]; 6
(1
): 100
PMID25998259
show ga
INTRODUCTION: Mesenchymal stem cells (MSCs) play a central role in the
remediation of cell and tissue damage. Erythropoietin (EPO) may enhance the
beneficial influence of MSCs during recovery from tissue and organ injuries.
Microvesicles (MVs) released from MSCs contribute to the restoration of kidney
damage. We studied the influence of EPO on MVs derived from MSCs, and the
protective effects of these factors in subjects with chronic kidney disease
(CKD). METHODS: The MVs derived from untreated MSCs (MSC-MVs) or from MSCs
incubated in different concentrations of EPO (1, 10, 100, and 500 IU/ml EPO-MVs)
were used to treat renal injury of unilateral ureteral obstruction (UUO) in vivo,
and transforming growth factor-?1 (TGF-?1)-induced fibrosis in a human renal
proximal tubular epithelial (HK2) cell line in vitro. Western blot and reverse
transcription polymerase chain reaction (RT-PCR) analyses were used to evaluate
the expression of epithelial and mesenchymal markers in the renal tissue and HK2
cells. Flow cytometry was used to assess apoptosis within the HK2 cells, and
microRNA (miRNA) microarray assays were used to determine the expression profiles
of miRNA in the MSC-MVs and EPO-MVs. RESULTS: Compared to MSC-MVs (untreated),
there was a significant increase in the number of EPO-MVs derived from MSCs
treated with 1-100 IU/ml EPO, and these EPO-MVs had a greater benefit in UUO mice
on days 7 and 14. Moreover, the EPO-MVs had a better restorative effect following
TGF-?1-induced fibrosis in HK2 cells at 24 h and 48 h. The flow cytometry results
revealed that both types of MVs, especially EPO-MVs, play an important
anti-apoptotic role in HK2 cells treated with TGF-?1. The miRNA profiles of the
MVs revealed that EPO-MVs changed 212 miRNAs (fold-change ? 1.5), including
miR-299, miR-499, miR-302, and miRNA-200, and that 70.28 % of these changes
involved upregulation. The changed miRNA in EPO-MVs may have contributed to their
enhanced protective effects following renal injury compared to MSC-MVs.
CONCLUSIONS: There was a dose-dependent increase in the level of EPO-MVs within
the range of 1-100 IU/ml EPO. Although both MSC-MVs and EPO-MVs protect the
kidney from fibrosis-related damage, there is a superior effect of EPO-MVs.
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