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2017 ; 16
(11
): 1112-1119
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gab.com Text
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English Wikipedia
Organoid cystogenesis reveals a critical role of microenvironment in human
polycystic kidney disease
#MMPMID28967916
Cruz NM
; Song X
; Czerniecki SM
; Gulieva RE
; Churchill AJ
; Kim YK
; Winston K
; Tran LM
; Diaz MA
; Fu H
; Finn LS
; Pei Y
; Himmelfarb J
; Freedman BS
Nat Mater
2017[Nov]; 16
(11
): 1112-1119
PMID28967916
show ga
Polycystic kidney disease (PKD) is a life-threatening disorder, commonly caused
by defects in polycystin-1 (PC1) or polycystin-2 (PC2), in which tubular
epithelia form fluid-filled cysts. A major barrier to understanding PKD is the
absence of human cellular models that accurately and efficiently recapitulate
cystogenesis. Previously, we have generated a genetic model of PKD using human
pluripotent stem cells and derived kidney organoids. Here we show that systematic
substitution of physical components can dramatically increase or decrease cyst
formation, unveiling a critical role for microenvironment in PKD. Removal of
adherent cues increases cystogenesis 10-fold, producing cysts phenotypically
resembling PKD that expand massively to 1-centimetre diameters. Removal of stroma
enables outgrowth of PKD cell lines, which exhibit defects in PC1 expression and
collagen compaction. Cyclic adenosine monophosphate (cAMP), when added, induces
cysts in both PKD organoids and controls. These biomaterials establish a highly
efficient model of PKD cystogenesis that directly implicates the microenvironment
at the earliest stages of the disease.