PMID- 23029541
OWN - NLM
STAT- MEDLINE
DCOM- 20130220
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 9
DP  - 2012
TI  - Renoprotective effect of human umbilical cord-derived mesenchymal stem cells in 
      immunodeficient mice suffering from acute kidney injury.
PG  - e46504
LID - 10.1371/journal.pone.0046504 [doi]
LID - e46504
AB  - It is unknown whether human umbilical cord-derived mesenchymal stem cells 
      (hUC-MSCs) can improve the renal function of patients suffering from acute kidney 
      injury. Moreover, before beginning clinical trials, it is necessary to 
      investigate this renoprotective effect of hUC-MSCs in a xenogeneic model of acute 
      kidney injury. However, no previous studies have examined the application of 
      hUC-MSCs to immunodeficient mice suffering from acute kidney injury. The 
      objectives of this study were to examine whether hUC-MSCs could improve renal 
      function in nonobese diabetic-severe combined immune deficiency (NOD-SCID) mice 
      suffering from acute kidney injury, and to investigate the mechanism(s) for 
      hUC-MSCs to improve renal function in this xenogeneic model. Early (3 hr) and 
      late (12 hr) administrations of hUC-MSCs (10(6) cells) were performed via the 
      external jugular vein into NOD-SCID mice suffering from either folic acid (FA) 
      (250 mg/kg body weight) or vehicle. The results showed that early administration 
      of hUC-MSCs improved the renal function of NOD-SCID mice suffering from 
      FA-induced acute kidney injury, as evidenced by decreased serum urea nitrogen and 
      serum creatinine levels, as well as a reduced tubular injury score. The 
      beneficial effects of hUC-MSCs were through reducing apoptosis and promoting 
      proliferation of renal tubular cells. These benefits were independent of 
      inflammatory cytokine effects and transdifferentiation. Furthermore, this study 
      is the first one to show that the reduced apoptosis of renal tubular cells by 
      hUC-MSCs in this xenogeneic model is mediated through the mitochondrial pathway, 
      and through the increase of Akt phosphorylation.
FAU - Fang, Te-Chao
AU  - Fang TC
AD  - Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan. 
      fangtechao@yahoo.com.tw
FAU - Pang, Cheng-Yoong
AU  - Pang CY
FAU - Chiu, Sheng-Chun
AU  - Chiu SC
FAU - Ding, Dah-Ching
AU  - Ding DC
FAU - Tsai, Rong-Kung
AU  - Tsai RK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120927
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, CD)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 935E97BOY8 (Folic Acid)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Acute Kidney Injury/blood/chemically induced/*therapy
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Apoptosis
MH  - Blood Urea Nitrogen
MH  - Caspases/metabolism
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Creatinine/blood
MH  - Cytokines/metabolism
MH  - Cytoprotection
MH  - Folic Acid
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Kidney Tubules/metabolism/pathology/physiopathology
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/metabolism/*physiology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Tissue Array Analysis
MH  - Umbilical Cord/cytology
MH  - Wharton Jelly/*cytology
PMC - PMC3459926
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/10/03 06:00
MHDA- 2013/02/21 06:00
PMCR- 2012/09/27
CRDT- 2012/10/03 06:00
PHST- 2012/02/13 00:00 [received]
PHST- 2012/09/03 00:00 [accepted]
PHST- 2012/10/03 06:00 [entrez]
PHST- 2012/10/03 06:00 [pubmed]
PHST- 2013/02/21 06:00 [medline]
PHST- 2012/09/27 00:00 [pmc-release]
AID - PONE-D-12-04486 [pii]
AID - 10.1371/journal.pone.0046504 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(9):e46504. doi: 10.1371/journal.pone.0046504. Epub 2012 Sep 27.