Login to Access Video or Poster Abstract: MP23-01
Sources of Funding: Wake Forest University Health Sciences, Internal funding via Pilot Award from the Hypertension & Vascular Research Center_x000D_ _x000D_

Introduction

Kidney function declines with age; older adults have renal function only 50-60% that of healthy young people. Most older patients have some degree of impaired renal function after renal surgery. Cell-based therapy is a promising alternative method to restore renal function in the treatment of chronic renal insufficiency. The goal of this study is to determine whether human urine-derived stem cells (USCs) can prompt renal tissue remolding in a rodent model of age-related kidney insufficiency.

Methods

Urine samples were obtained from healthy men (n=6, 28-35 years old). USCs were isolated and expanded at passage 5. Eighteen male SD rats (50-62 week old) with renal insufficiency (increased levels of urine protein and serum creatinine) were divided into 3 groups (G). G1, animals received 5 intravenous cell implantations of 2 x106 cells/0.2 ml serum-free medium /rat/time period weekly; G2, as in G1 but intraperitoneally delivered; G3, as in G1 but serum-free medium alone. Healthy male SD rats at the same age were controls.

Results

Cultured USCs secreted >20 kinds of trophic factors, including high levels of matrix metallopeptidase 9, which is involved in extracellular matrix degradation. Histologic and immunocytochemical staining showed that ED1 (inflammatory marker), alpha-smooth muscle actin (myofibroblast marker), and collagen deposition were significantly less within the medulla or cortex in rats with renal insufficiency vs. controls. G1 and G2 rats showed significantly inhibited inflammation and fibrosis in interstitial tissue, and reduced collagen deposits around renal vessels and the basement membrane of renal tubule and glomerular tissue, compared to G3.

Conclusions

Renal fibrosis is potentially reversible and therapeutic use of USCs can reverse specifically targeted decrease of influx of inflammatory macrophages, interstitial fibrosis formation and collagen deposition through their paracrine effects. Implantation of USCs has potential in the prevention and treatment of renal insufficiency. _x000D_

Funding

Wake Forest University Health Sciences, Internal funding via Pilot Award from the Hypertension & Vascular Research Center_x000D_ _x000D_