title: Ischemia/reperfusion-induced renal failure in rats as a model for evaluating cell therapies.
abstract: Chronic renal failure is a devastating disease that leads to a multitude of complications. Cell therapy has emerged as a potential treatment modality for renal failure. However, efficacy testing on systemic renal function has been challenging due to the limited availability of reliable models that are fully characterized. In this study, we investigated the possibility of using renal ischemia/reperfusion (I/R) injury as a viable model for testing cell therapies. We examined functional and pathological changes in rat kidneys that were exposed to different ischemia times. Male Lewis rats were divided into five groups. Renal failure was induced by clamping both renal pedicles for combinations of 60, 75, and 90 min, followed by reperfusion. Age-matched healthy rats served as controls. Blood was collected at regular intervals for serum chemistry, and kidneys were harvested at the same intervals for histomorphological assessment. Serum creatinine levels of the animals with I/R injury increased significantly after 3 days and returned to normal levels at 4 weeks. Histologically, kidney tissue showed progressive glomerular and tubular deterioration with varying degrees of fibrosis. Animals exposed to 75- and 90-min ischemia combination times consistently generated more severe injury than the 60-min ischemia period. However, these groups resulted in a high mortality rate. A model in which one kidney is exposed to a shorter ischemia time (60 or 90 min) resulted in sustained renal damage with a lower mortality rate. This study shows that kidneys exposed to I/R result in renal tissue damage as well as decreased renal function. This model can be used to study both the short-term and longer-term effects of kidney disease by varying the length of the ischemic time. In particular, the use of longer ischemic times (75 and 90 min) could be used to study new therapies for acute renal disease, whereas shorter ischemic times (60 min) could be used to study therapies for chronic renal insufficiency.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Wang
authors.forename: Adam
authors.initials: A
authors.lastname: Varner
authors.forename: Tamer
authors.initials: T
authors.lastname: AbouShwareb
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.forename: James J
authors.initials: JJ
authors.lastname: Yoo
mesh_terms: D000818:Animals; D017690:Cell Transplantation; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D007668:Kidney / Q000098:blood supply*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D051437:Renal Insufficiency / Q000209:etiology / Q000601:surgery*; D015427:Reperfusion Injury / Q000150:complications