Presentation Authors: Chao Zhang, Sunil K George, Mehran Abolbashar, Tae-Hyoung Kim, In Kap Ko, Yuanyuan Zhang*, John Jackson, Sang Jin Lee, James J Yoo, Anthony Atala, Winston Salem, NC
Introduction: Drug-induced nephrotoxicity often occurs in the patients with existing renal dysfunction or renal ischemia, potentially leading to chronic kidney disease (CKD). Prompt treatment of drug induced adverse effects is critical to prevent progression to end-stage renal disease. The goal of this study was to demonstrate the therapeutic potential of urine-derived stem cells (USC) to treat chronic kidney disease-induced by nephrotoxic drug and renal ischemia.
Methods: Human USC were collected, expanded and identified by flow cytometry analysis. The CKD model was induced by creating an ischemia-reperfusion injury followed by gentamicin injection. Twenty-eight immune deficient rats were divided into three groups: phosphate-buffered saline (PBS)-treated group (n=9), USC-treated group (n=9), and sham group with age-matched controls (n=10). Cell suspension of USC or PBS was bilaterally injected into the renal parenchyma (50x10^6/100Âµl/kidney) 9 weeks after the CKD model creation. Blood and urine samples were collected to test renal function (i.e, serum creatinine levels and glomerulus filtration rate). The kidneys were harvested 12 weeks after cell injection. Histologically, the number of affected glomeruli and tubular atrophy, levels of collagen deposition, interstitial fibrosis and inflammatory monocyte infiltration were examined.
Results: The USC used in this study expressed CD24+, CD29+, CD44+, CD90+, CD105+, CD146+, and SSEA4+ but did not express CD31, CD34, CD45 and STRO-1. Renal function in the animals treated with USC was significantly improved, as compared to those in the PBS-treated animals (p < 0.05). The number of glomerular sclerosis and atrophic renal tubulars, amount of fibrotic area and monocyte infiltration significantly decreased in the USC-treated group as compared to the PBS group (p < 0.05).
Conclusions: The present study demonstrates the nephron-protective effect of USC on renal function via anti-inflammatory and anti-fibrotic activity in a rat model, which provides an alternative treatment option for CKD.