Klotho is a protein primarily expressed in renal tubular epithelial cells. 
Studies have suggested that Klotho is an antiaging protein that reduces renal 
fibrosis after acute kidney injury (AKI) and inhibits stem cell senescence. Bone 
marrow mesenchymal stem cells (BMSCs) have consistent proliferation ability and 
multidirectional differentiation ability and have been used to treat tissue 
injury. Thus, we hypothesized that Klotho expressed in BMSCs could increase the 
renal protective effects of BMSCs. To verify the hypothesis, we isolated BMSCs 
from C57BL/6 mice, transfected them with Klotho-GFP-adenovirus and investigated 
the change in BMSC proliferation. We then transplanted Klotho-GFP-BMSCs into 
mice with AKI and investigated the therapeutic effect compared with that of 
sham-treated mice and GFP-BMSC-transplanted mice. Kidney fibrosis after 
ischemia/reperfusion injury (IRI) was relieved by BMSC transplantation, and the 
antifibrotic effect of BMSCs was significantly enhanced by overexpressing the 
Klotho gene. Mechanistic studies showed that Klotho increased pluripotency gene 
expression in BMSCs. Klotho produced by Klotho-GFP-BMSCs inhibited the 
Wnt/β-catenin pathway in renal tubular epithelial cells (TECs). Klotho-GFP-BMSCs 
showed increased proliferative ability and more potent immuno-regulation ability 
than did GFP-BMSCs. Our findings suggested that Klotho gene-modified BMSCs may 
be a better choice for cell therapy after AKI.