2253 HUMAN KIDNEY CELL CULTURES CONTAINING ERYTHROPOIETIN-PRODUCING CELLS AMELIORATE RENAL FUNCTION IN THE CHRONIC KIDNEY INJURY MODEL (2011)

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Vascular Surgery1 Apr 20112253 HUMAN KIDNEY CELL CULTURES CONTAINING ERYTHROPOIETIN-PRODUCING CELLS AMELIORATE RENAL FUNCTION IN THE CHRONIC KIDNEY INJURY MODEL Liliya M. Yamaleyeva, Nadia K. Guimaraes-Souza, Louis S. Krane, Anthony Atala, Tamer Aboushwareb, and James J. Yoo Liliya M. YamaleyevaLiliya M. Yamaleyeva Winston-Salem, NC More articles by this author , Nadia K. Guimaraes-SouzaNadia K. Guimaraes-Souza Winston-Salem, NC More articles by this author , Louis S. KraneLouis S. Krane Winston-Salem, NC More articles by this author , Anthony AtalaAnthony Atala Winston-Salem, NC More articles by this author , Tamer AboushwarebTamer Aboushwareb Winston-Salem, NC More articles by this author , and James J. YooJames J. Yoo Winston-Salem, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2495AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The increase in chronic kidney disease (CKD) cases and reduced availability of treatment for CKD patients calls for the development of new therapeutic modalities. We previously have demonstrated that renal cells isolated from rodents are able to stably express erythropoietin (EPO) and that these cells possess the ability to regulate EPO expression in response to varying levels of oxygen tension. In this study we investigated whether human primary kidney cultures (hPKC) containing EPO-producing cells could be used for cell therapy and improve renal function in a chronic kidney injury model. METHODS hPKC cultures were established from discarded human kidneys (Carolina Donor Services, NC). hPKCs were characterized for EPO, Tamm-Horsfall (THP), CD73, and podocin by immunofluorescent staining (IF). Renal ischemia was achieved by clamping renal pedicles bilaterally for 60 minutes followed by reperfusion (IR). Two weeks post-IR injury, gentamicin (GM) was administered (100 mg/kg) to establish a chronic kidney injury in the nude rats. Human PKC or hPKC enriched in EPO-producing fibroblast-like cells (F+) via anti-fibroblast antibodies (Miltenyi Biotech), were injected bilaterally into the renal parenchyma. Serum creatinine and hemoglobin were measured by standard assays. Urinary albumin and Kim-1 were determined using Meso Scale Discovery technology. CD68+ cells were determined by immunostaining, and collagen deposition - by Masson's trichrome staining. RESULTS The IR-GM injury resulted in significantly elevated serum creatinine, anemia, and renal fibrosis [*p<0.05; n=6]. Prior to in vivo delivery THP, podocin, and CD73 were confirmed within the PKC. As shown by FACS analysis, EPO protein was at ∼30% of hPKC population, and was further enriched to ∼66% in hPKC (F+). hPKC or hPKC (F+) improved renal function as shown by reduced serum creatinine (*p<0.05 vs. vehicle; n=4–6) as compared to vehicle control. Renal injury was improved as characterized by reduced urinary albumin, KIM-1, total collagen deposition, number of tubular casts and CD68-positive cells (*p<0.05 vs. vehicle, n=4–6). CONCLUSIONS Cell therapy with either hPKC or hPKC (F+) cells improved indices of renal function and injury when delivered to the renal parenchyma of IR-GM rats, a chronic kidney injury model. These data support the possibility of using EPO-producing human kidney cells as components of cell-based therapies for degenerative kidney diseases. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185 Issue 4S April 2011 Page: e903-e904 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Metrics Author Information Liliya M. Yamaleyeva Winston-Salem, NC More articles by this author Nadia K. Guimaraes-Souza Winston-Salem, NC More articles by this author Louis S. Krane Winston-Salem, NC More articles by this author Anthony Atala Winston-Salem, NC More articles by this author Tamer Aboushwareb Winston-Salem, NC More articles by this author James J. Yoo Winston-Salem, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...