Modeling the prostate stem cell niche: an evaluation of stem cell survival and expansion in vitro.
The goal of this work was to engineer a clinically relevant in vitro model of human prostate stem cells (PSCs) that could be used to interrogate the mechanisms of stem cell control. We, therefore, compared the growth potential of stem cells in 3D culture (where the conditions would favor a quiescent state) with monolayer culture that has previously been demonstrated to induce PSC division. We found a fundamental difference between cultures of primary, adult PSCs grown as monolayers compared to those grown as spheres. The first supported the expansion and maintenance of PSCs from single cells while the latter did not. In an attempt to determine the mechanisms governing stem cell control, several known stem cell activators (including IFNalpha, FGF2, anti-TGFbeta, and dihydrotestosterone) were studied. However, cell division was not observed. CD133+ cells derived from a prostate cell line did not grow as spheres from single cells but did grow from aggregates. We conclude that PSCs can be expanded and maintained in monolayer culture from single cells, but that PSCs are growth quiescent when grown as spheres. It is likely that the physical arrangement of cells in monolayer provides an injury-type response, which can activate stem cells into cycle.
Lang
Shona H
SH
YCR Cancer Research Unit, Department of Biology, University of York, Heslington, York, United Kingdom.
Anderson
Elizabeth
E
Fordham
Robert
R
Collins
Anne T
AT
D000071916:AC133 Antigen; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010455:Peptides / Q000378:metabolism; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D055153:Stem Cell Niche / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000276:immunology
D000071916:AC133 Antigen; D000906:Antibodies; D015703:Antigens, CD; D006023:Glycoproteins; D016898:Interferon-alpha; C000606023:PROM1 protein, human; D010455:Peptides; D016212:Transforming Growth Factor beta; D013196:Dihydrotestosterone; D016222:Fibroblast Growth Factor 2