title: Induced pluripotent stem cells without c-Myc attenuate acute kidney injury via downregulating the signaling of oxidative stress and inflammation in ischemia-reperfusion rats.
abstract: Induced pluripotent stem (iPS) cells have potential for multilineage differentiation and provide a resource for stem cell-based treatment. However, the therapeutic effect of iPS cells on acute kidney injury (AKI) remains uncertain. Given that the oncogene c-Myc may contribute to tumorigenesis  by causing genomic instability, herein we evaluated the therapeutic effect of iPS cells without exogenously introduced c-Myc on ischemia-reperfusion (I/R)-induced AKI. As compared with phosphate-buffered saline (PBS)-treated group, administration of iPS cells via intrarenal arterial route  into kidneys improved the renal function and attenuated tubular injury score at 48 h after ischemia particularly at the dose of 5 × 10(5) iPS cells. However, a larger number of iPS cells (5 × 10(7) per rat) diminished the therapeutic effects for AKI and profoundly  reduced renal perfusion detected by laser Doppler imaging in the reperfusion phase. In addition, the green fluorescence protein-positive iPS cells mobilized to the peritubular area at 48 h following ischemia, accompanied by a significant reduction in infiltration of macrophages and apoptosis  of tubular cells, and a remarkable enhancement in endogenous tubular cell proliferation. Importantly, transplantation of iPS cells reduced the expression of oxidative substances, proinflammatory cytokines, and apoptotic factors in I/R kidney tissues and eventually improved survival in rats  of ischemic AKI. Six months after transplantation in I/R rats, engrafted iPS cells did not result in tumor formation in kidney and other organs. In summary, considering the antioxidant, anti-inflammatory, and antiapoptotic properties of iPS cells without c-Myc, transplantation of such cells  may be a treatment option for ischemic AKI.
authors.affiliation: Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pei-Ying
authors.initials: PY
authors.lastname: Lee
authors.forename: Yueh
authors.initials: Y
authors.lastname: Chien
authors.forename: Guang-Yuh
authors.initials: GY
authors.lastname: Chiou
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Chih-Hwa
authors.initials: CH
authors.lastname: Chiou
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Tarng
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000401:mortality / Q000628:therapy*; D000818:Animals; D017209:Apoptosis; D001806:Blood Urea Nitrogen; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D015996:Survival Rate
chemical_list: D016207:Cytokines; D016271:Proto-Oncogene Proteins c-myc