RGD Reference Report - Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia-reperfusion injury. - Rat Genome Database

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Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia-reperfusion injury.

Authors: Chen, YT  Yang, CC  Zhen, YY  Wallace, CG  Yang, JL  Sun, CK  Tsai, TH  Sheu, JJ  Chua, S  Chang, CL  Cho, CL  Leu, S  Yip, HK 
Citation: Chen YT, etal., Stem Cell Res Ther. 2013 May 31;4(3):62.
RGD ID: 8693706
Pubmed: PMID:23726287   (View Abstract at PubMed)
PMCID: PMC3706768   (View Article at PubMed Central)
DOI: DOI:10.1186/scrt212   (Journal Full-text)

INTRODUCTION: This study tested the hypothesis that cyclosporine (CsA)-supported syngeneic adipose-derived mesenchymal stem cell (ADMSC) therapy offered superior attenuation of acute ischemia-reperfusion (IR) kidney injury to either therapy alone. METHODS: Adult Sprague-Dawley rats (n = 40) were equally divided into group 1 (sham controls), group 2 (IR injury), group 3 (IR + CsA (20 mg/kg at 1 and 24 hours after procedure)), group 4 (syngeneic ADMSC (1.2x106) at 1, 6 and 24 hours after procedure), and group 5 (IR + CsA-ADMSC). RESULTS: By 72 hours after the IR procedure, the creatinine level and the ratio of urine protein to creatinine were highest in group 2 and lowest in group 1, and significantly higher in groups 3 and 4 than in group 5 (all P <0.05 for inter-group comparisons), but showed no differences between groups 3 and 4 (P >0.05). The inflammatory biomarkers at mRNA (matrix metalloproteinase-9, RANTES, TNF-alpha), protein (TNF-alpha, NF-kappaB, intercellular adhesion molecule-1, platelet-derived growth factor), and cellular (CD68+) levels of IR kidney showed a similar pattern compared with that of creatinine in all groups (all P <0.05 for inter-group comparisons). The protein expressions of oxidative stress (oxidized protein), reactive oxygen species (NADPH oxidases NOX-1, NOX-2), apoptosis (Bcl-2-associated X protein, caspase-3 and poly(ADP-ribose) polymerase) and DNA damage (phosphorylated H2A histone family member X-positive, proliferating cell nuclear antigen-positive cells) markers exhibited a pattern similar to that of inflammatory mediators amongst all groups (all P <0.05 for inter-group comparisons). Expressions of antioxidant biomarkers at cellular (glutathione peroxidase, glutathione reductase, heme oxygenase-1 (HO-1)) and protein (NADPH dehydrogenase (quinone)-1, HO-1, endothelial nitric oxide synthase) levels, and endothelial progenitor cell markers (C-X-C chemokine receptor type 4-positive, stromal cell-derived factor-1alpha-positive) were lowest in groups 1 and 2, higher in groups 3 and 4, and highest in group 5 (all P <0.05 for inter-group comparisons). CONCLUSION: Combination therapy using CsA plus ADMSCs offers improved protection against acute IR kidney injury.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
H2AXHumanKidney Reperfusion Injury treatmentISOH2ax (Rattus norvegicus) RGD 
H2axMouseKidney Reperfusion Injury treatmentISOH2ax (Rattus norvegicus) RGD 
H2axRatKidney Reperfusion Injury treatmentIEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
H2ax  (H2A.X variant histone)

Genes (Mus musculus)
H2ax  (H2A.X variant histone)

Genes (Homo sapiens)
H2AX  (H2A.X variant histone)


Additional Information