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The presence of human mesenchymal stem cells of renal origin in amniotic fluid
increases with gestational time
#MMPMID29695308
Rahman MS
; Spitzhorn LS
; Wruck W
; Hagenbeck C
; Balan P
; Graffmann N
; Bohndorf M
; Ncube A
; Guillot PV
; Fehm T
; Adjaye J
Stem Cell Res Ther
2018[Apr]; 9
(1
): 113
PMID29695308
show ga
BACKGROUND: Established therapies for managing kidney dysfunction such as kidney
dialysis and transplantation are limited due to the shortage of compatible
donated organs and high costs. Stem cell-based therapies are currently under
investigation as an alternative treatment option. As amniotic fluid is composed
of fetal urine harboring mesenchymal stem cells (AF-MSCs), we hypothesized that
third-trimester amniotic fluid could be a novel source of renal progenitor and
differentiated cells. METHODS: Human third-trimester amniotic fluid cells (AFCs)
were isolated and cultured in distinct media. These cells were characterized as
renal progenitor cells with respect to cell morphology, cell surface marker
expression, transcriptome and differentiation into chondrocytes, osteoblasts and
adipocytes. To test for renal function, a comparative albumin endocytosis assay
was performed using AF-MSCs and commercially available renal cells derived from
kidney biopsies. Comparative transcriptome analyses of first, second and third
trimester-derived AF-MSCs were conducted to monitor expression of renal-related
genes. RESULTS: Regardless of the media used, AFCs showed expression of
pluripotency-associated markers such as SSEA4, TRA-1-60, TRA-1-81 and C-Kit. They
also express the mesenchymal marker Vimentin. Immunophenotyping confirmed that
third-trimester AFCs are bona fide MSCs. AF-MSCs expressed the master renal
progenitor markers SIX2 and CITED1, in addition to typical renal proteins such as
PODXL, LHX1, BRN1 and PAX8. Albumin endocytosis assays demonstrated the
functionality of AF-MSCs as renal cells. Additionally, upregulated expression of
BMP7 and downregulation of WT1, CD133, SIX2 and C-Kit were observed upon
activation of WNT signaling by treatment with the GSK-3 inhibitor CHIR99201.
Transcriptome analysis and semiquantitative PCR revealed increasing expression
levels of renal-specific genes (e.g., SALL1, HNF4B, SIX2) with gestational time.
Moreover, AF-MSCs shared more genes with human kidney cells than with native MSCs
and gene ontology terms revealed involvement of biological processes associated
with kidney morphogenesis. CONCLUSIONS: Third-trimester amniotic fluid contains
AF-MSCs of renal origin and this novel source of kidney progenitors may have
enormous future potentials for disease modeling, renal repair and drug screening.
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