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2017 ; 6
(2
): 405-418
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Clinical-Grade Isolated Human Kidney Perivascular Stromal Cells as an Organotypic
Cell Source for Kidney Regenerative Medicine
#MMPMID28191776
Leuning DG
; Reinders ME
; Li J
; Peired AJ
; Lievers E
; de Boer HC
; Fibbe WE
; Romagnani P
; van Kooten C
; Little MH
; Engelse MA
; Rabelink TJ
Stem Cells Transl Med
2017[Feb]; 6
(2
): 405-418
PMID28191776
show ga
Mesenchymal stromal cells (MSCs) are immunomodulatory and tissue homeostatic
cells that have shown beneficial effects in kidney diseases and transplantation.
Perivascular stromal cells (PSCs) identified within several different organs
share characteristics of bone marrow-derived MSCs (BM-MSCs). These PSCs may also
possess tissue-specific properties and play a role in local tissue homeostasis.
We hypothesized that human kidney-derived PSCs (hkPSCs) would elicit improved
kidney repair in comparison with BM-MSCs. Here we introduce a novel,
clinical-grade isolation method of hkPSCs from cadaveric kidneys by enriching for
the perivascular marker, NG2. hkPSCs show strong transcriptional similarities to
BM-MSCs but also show organotypic expression signatures, including the HoxD10 and
HoxD11 nephrogenic transcription factors. Comparable to BM-MSCs, hkPSCs showed
immunosuppressive potential and, when cocultured with endothelial cells, vascular
plexus formation was supported, which was specifically in the hkPSCs accompanied
by an increased NG2 expression. hkPSCs did not undergo myofibroblast
transformation after exposure to transforming growth factor-?, further
corroborating their potential regulatory role in tissue homeostasis. This was
further supported by the observation that hkPSCs induced accelerated repair in a
tubular epithelial wound scratch assay, which was mediated through hepatocyte
growth factor release. In vivo, in a neonatal kidney injection model, hkPSCs
reintegrated and survived in the interstitial compartment, whereas BM-MSCs did
not show this potential. Moreover, hkPSCs gave protection against the development
of acute kidney injury in vivo in a model of rhabdomyolysis-mediated
nephrotoxicity. Overall, this suggests a superior therapeutic potential for the
use of hkPSCs and their secretome in the treatment of kidney diseases. Stem Cells
Translational Medicine 2017;6:405-418.