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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Transl+Med
2017 ; 15
(1
): 147
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Transplantation of human fetal pancreatic progenitor cells ameliorates renal
injury in streptozotocin-induced diabetic nephropathy
#MMPMID28655312
Jiang Y
; Zhang W
; Xu S
; Lin H
; Sui W
; Liu H
; Peng L
; Fang Q
; Chen L
; Lou J
J Transl Med
2017[Jun]; 15
(1
): 147
PMID28655312
show ga
BACKGROUND: Diabetic nephropathy (DN) is a severe complication of diabetes
mellitus (DM). Pancreas or islet transplantation has been reported to prevent the
development of DN lesions and ameliorate or reverse existing glomerular lesions
in animal models. Shortage of pancreas donor is a severe problem. Islets derived
from stem cells may offer a potential solution to this problem. OBJECTIVE: To
evaluate the effect of stem cell-derived islet transplantation on DN in a rat
model of streptozotocin-induced DM. METHODS: Pancreatic progenitor cells were
isolated from aborted fetuses of 8 weeks of gestation. And islets were prepared
by suspension culture after a differentiation of progenitor cells in medium
containing glucagon-like peptide-1 (Glp-1) and nicotinamide. Then islets were
transplanted into the liver of diabetic rats via portal vein. Blood glucose,
urinary volume, 24 h urinary protein and urinary albumin were measured once
biweekly for 16 weeks. Graft survival was evaluated by monitoring human C-peptide
level in rat sera and by immunohistochemical staining for human mitochondrial
antigen and human C-peptide in liver tissue. The effect of progenitor-derived
islets on filtration membrane was examined by electron microscopy and real-time
polymerase chain reaction (PCR). Immunohistochemical staining, real-time PCR and
western blot were employed for detecting fibronectin, protein kinase C beta
(PKC?), protein kinase A (PKA), inducible nitric oxide synthase (iNOS) and
superoxide dismutase (SOD). RESULTS: Islet-like clusters derived from 8th
gestational-week human fetal pancreatic progenitors survived in rat liver. And
elevated serum level of human C-peptide was detected. Blood glucose, 24 h urinary
protein and urinary albumin were lower in progenitor cell group than those in DN
or insulin treatment group. Glomerular basement membrane thickness and
fibronectin accumulation decreased significantly while podocytes improved
morphologically in progenitor cell group. Furthermore, receptor of advanced
glycation end products and PKC? became down-regulated whereas PKA up-regulated by
progenitor cell-derived islets. And iNOS rose while SOD declined. CONCLUSIONS: DN
may be reversed by transplantation of human fetal pancreatic progenitor
cell-derived islets. And fetal pancreatic progenitor cells offer potential
resources for cell replacement therapy.
|*Stem Cell Transplantation
[MESH]
|Albuminuria/blood/complications/pathology
[MESH]
|Animals
[MESH]
|Blood Glucose/metabolism
[MESH]
|Cell Survival
[MESH]
|Cyclic AMP-Dependent Protein Kinases/metabolism
[MESH]