title: Enhanced renoprotective effect of HIF-1α modified human adipose-derived stem cells on cisplatin-induced acute kidney injury in vivo.
abstract: Current therapeutic options for acute kidney injury (AKI) are limited to the use of supportive measures and dialysis. A recent approach that has sparked great interest and gained enormous popularity is the implantation of stem cells to repair acutely damaged kidney organ. Hypoxia inducible factor-1α (HIF-1α) is effective in protecting the kidney from ischemia and nephrotoxicity. In this study, we investigated whether HIF-1α-modified adipose-derived stem cells (ASCs) had an enhanced protective effect on cisplatin-induced kidney injury in vivo. Cisplatin-induced AKI was established in nude mice. Our study demonstrated that HIF-1α-modified ASCs obviously promoted the recovery of renal function, ameliorated the extent of histologic injury and reduced renal apoptosis and inflammation, but HIF-1α-modified ASCs homed to kidney tissues at very low levels after transplantation. In addition, we also found that HIF-1α-modified ASCs significantly increased HO-1 expression in cisplatin-induced AKI in vivo. Thus, our study indicated HIF-1α-modified ASCs implantation could provide advanced benefits in the protection again AKI, which will contribute to developing a new therapeutic strategy for the treatment of AKI.
authors.affiliation: Nephrology Division, Jimin Hospital, Shanghai 200052, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Wang
authors.affiliation: Nephrology Division, Jimin Hospital, Shanghai 200052, China.
authors.forename: Ze-Zheng
authors.initials: ZZ
authors.lastname: Li
authors.affiliation: Nephrology Division, Jimin Hospital, Shanghai 200052, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Nephrology Division, Jimin Hospital, Shanghai 200052, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Nephrology Division, Jimin Hospital, Shanghai 200052, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Nephrology Division, Jimin Hospital, Shanghai 200052, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Lu
authors.affiliation: Nephrology Division, Jimin Hospital, Shanghai 200052, China.
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Zhang
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D017209:Apoptosis; D002945:Cisplatin / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000637:transplantation; D018836:Inflammation Mediators / Q000378:metabolism; D007677:Kidney Function Tests
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018836:Inflammation Mediators; D051547:Heme Oxygenase-1; D002945:Cisplatin