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Embryonic Stem Cells Proliferate and Differentiate when Seeded into Kidney Scaffolds

Edward A. Ross^*, Matthew J. Williams, Takashi Hamazaki, Naohiro Terada, William L. Clapp, Christopher Adin, Gary W. Ellison, Marda Jorgensen^|| and Christopher D. Batich^¶

*Division of Nephrology, Hypertension and Transplantation,
Department of Biomedical Engineering,
Department of Pathology,
Department of Small Animal Clinical Sciences,
^||Department of Regenerative Medicine, and
^¶Department of Materials Science and Engineering, University of Florida, Gainesville, Florida

Correspondence: Dr. Edward A. Ross, Division of Nephrology, Hypertension and Transplantation, University of Florida, Box 100224, Gainesville, FL 32610-0224. Phone: +352-273-8822; Fax: +352-392-3581; E-mail: rossea{at}medicine.ufl.edu

Received for publication November 21, 2008. Accepted for publication July 22, 2009.

The scarcity of transplant allografts for diseased organs has prompted efforts at tissue regeneration using seeded scaffolds, an approach hampered by the enormity of cell types and complex architectures. Our goal was to decellularize intact organs in a manner that retained the matrix signal for differentiating pluripotent cells. We decellularized intact rat kidneys in a manner that preserved the intricate architecture and seeded them with pluripotent murine embryonic stem cells antegrade through the artery or retrograde through the ureter. Primitive precursor cells populated and proliferated within the glomerular, vascular, and tubular structures. Cells lost their embryonic appearance and expressed immunohistochemical markers for differentiation. Cells not in contact with the basement membrane matrix became apoptotic, thereby forming lumens. These observations suggest that the extracellular matrix can direct regeneration of the kidney, and studies using seeded scaffolds may help define differentiation pathways.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673