Cell therapy with human renal cell cultures containing erythropoietin-positive cells improves chronic kidney injury

Liliya M. Yamaleyeva, Nadia K. Guimaraes-Souza, Louis S. Krane, Sigrid Agcaoili, Kenneth Gyabaah, Anthony Atala, Tamer Aboushwareb, James J. Yoo

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

New therapeutic strategies for chronic kidney disease (CKD) are necessary to offset the rising incidence of CKD and donor shortage. Erythropoietin (EPO), a cytokine produced by fibroblast-like cells in the kidney, has recently emerged as a renoprotective factor with anti-inflammatory, antioxidant properties. This study (a) determined whether human renal cultures (human primary kidney cells [hPKC]) can be enriched in EPO-positive cells (hPKC(F+)) by using magnetic-bead sorting; (b) characterized hPKC(F+) following cell separation; and (c) established that intrarenal delivery of enriched hPKC(F+) cells would be more beneficial in treatment of renal injury, inflammation, and oxidative stress than unsorted hPKC cultures in a chronic kidney injury model. Fluorescence-activated cell sorting analysis revealed higher expression of EPO (36%) and CD73 (27%) in hPKC(F+) as compared with hPKC. After induction of renal injury, intrarenal delivery of hPKC(F+) or hPKC significantly reduced serum creatinine, interstitial fibrosis in the medulla, and abundance of CD68-positive cells in the cortex and medulla (p <. 05). However, only hPKC(F+) attenuated interstitial fibrosis in the renal cortex and decreased urinary albumin (3.5-fold) and urinary tubular injury marker kidney injury molecule 1 (16-fold). hPKC(F+) also significantly reduced levels of renal cortical monocyte chemotactic protein 1 (1.8-fold) and oxidative DNA marker 8-hydroxy-deoxyguanosine (8-OHdG) (2.4-fold). After 12 weeks, we detected few injected cells, which were localized mostly to the cortical interstitium. Although cell therapy with either hPKC(F+) or hPKC improved renal function, the hPKC(F+) subpopulation provides greater renoprotection, perhaps through attenuation of inflammation and oxidative stress. We conclude that hPKC(F+) may be used as components of cell-based therapies for degenerative kidney diseases.

Original languageEnglish (US)
Pages (from-to)373-383
Number of pages11
JournalStem Cells Translational Medicine
Volume1
Issue number5
DOIs
StatePublished - 2012

Keywords

  • Adult stem cells
  • Autologous stem cell transplantation
  • Cell biology
  • Cellular therapy
  • Erythropoietin
  • Renal fibrosis
  • Tissue-specific stem cells

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Medicine(all)

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  • Cite this

    Yamaleyeva, L. M., Guimaraes-Souza, N. K., Krane, L. S., Agcaoili, S., Gyabaah, K., Atala, A., Aboushwareb, T., & Yoo, J. J. (2012). Cell therapy with human renal cell cultures containing erythropoietin-positive cells improves chronic kidney injury. Stem Cells Translational Medicine, 1(5), 373-383. https://doi.org/10.5966/sctm.2011-0048