Open AccessCharacterization of Adult Prostatic Progenitor/Stem Cells Exhibiting Self‐Renewal and Multilineage Differentiation
Author(s) -
Barclay Wendy W.,
Axanova Linara S.,
Chen Wenhong,
Romero Lina,
Maund Sophia L.,
Soker Shay,
Lees Cynthia J.,
Cramer Scott D.
Publication year - 2008
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2007-0309
Subject(s) - biology , stem cell , mesenchyme , progenitor cell , microbiology and biotechnology , cellular differentiation , adult stem cell , stem cell marker , progenitor , mesenchymal stem cell , biochemistry , gene
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.