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TISSUE-SPECIFIC STEM CELLS

Characterization of Adult Prostatic Progenitor/Stem Cells Exhibiting Self-Renewal and Multilineage Differentiation

Departments of ^aCancer Biology and
^cPathology and
^bInstitute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

Key Words. Adult stem cells • Cell culture • Clonal assays • Self-renewal

Correspondence: Scott D. Cramer, Ph.D., Department of Cancer Biology, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA. Telephone: 336-713-7651; Fax: 336-713-7661; e-mail: scramer{at}wfubmc.edu

Received April 25, 2007; accepted for publication November 19, 2007.
First published online in STEM CELLS EXPRESS   November 29, 2007.



Demonstration of the hallmarks of stem cells, self-renewal and multilineage differentiation, is a challenge that has not been met for numerous tissues postulated to possess adult stem cells, including prostate tissue. Using a defined medium, we reproducibly isolated and maintained adult mouse prostatic cells with characteristics of progenitor/stem cells. Clonal populations of cells demonstrated tissue-specific multilineage differentiation by their ability to generate organized prostatic ductal structures in vivo, with luminal and basal cell layers, when grafted under the renal capsules of mice in the presence of fetal rat urogenital mesenchyme. Complete differentiation was demonstrated by the expression and secretion of terminally differentiated prostatic secretory products into the lumens. Self-renewal was demonstrated by serial transplantation of clonal populations that generated fully differentiated ductal structures in vivo. In vitro, undifferentiated cells expressed markers associated with prostate stem cells, including Sca 1 and CD49f, as well as basal cell markers (p63 and cytokeratins 5 and 14) and, at a low level, luminal cell markers (androgen receptor and cytokeratins 8 and 18). When grafted and allowed to differentiate in the presence of fetal urogenital mesenchyme, the cells differentiated into luminal cells and basal cells with more restricted protein expression patterns. These studies are the first to report a reproducible system to assess adult prostatic progenitor/stem cells.

Disclosure of potential conflicts of interest is found at the end of this article.