TY - JOUR
T1 - Mesenchymal stem cells and the embryonic reawakening theory of BPH
AU - Brennen, W. Nathaniel
AU - Isaacs, John T.
N1 - Funding Information:
The authors thank B. Zhang and I. P. Garraway (University of California–Los Angeles) for generously providing urogenital sinus tissue, A. Meeker for his assistance in developing the immunofluorescence assays, and the Sidney Kimmel Comprehensive Cancer Center (SKCCC) Immunohistochemistry Core supported by the SKCCC Cancer Center Support Grant (CCSG; P30 CA006973). The authors also acknowledge the following sources of financial support: the Prostate Cancer Foundation Young Investigator Award (W.N.B.), SKCCC CCSG developmental funds (P30 CA006973 (W.N.B.)), the U.S. Department of Defense (W81XWH-17-1-0528 (W.N.B.)), and the US NIH Prostate SPORE Grant (P50 CA058236 (J.T.I.)).
Publisher Copyright:
© 2018, Springer Nature Limited.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - The prostate is the only organ in a man that continues to grow with age. John McNeal proposed, 40 years ago, that this BPH is characterized by an age-related reinitiation of benign neoplastic growth selectively in developmentally abortive distal ducts within the prostate transition–periurethral zone (TPZ), owing to a reawakening of inductive stroma selectively within these zones. An innovative variant of this hypothesis is that, owing to its location, the TPZ is continuously exposed to urinary components and/or autoantigens, which produces an inflammatory TPZ microenvironment that promotes recruitment of bone marrow-derived mesenchymal stem cells (MSCs) and generates a paracrine-inductive stroma that reinitiates benign neoplastic nodular growth. In support of this hypothesis, MSCs infiltrate human BPH tissue and have the ability to stimulate epithelial stem cell growth. These results provide a framework for defining both the aetiology of BPH in ageing men and insights into new therapeutic approaches.
AB - The prostate is the only organ in a man that continues to grow with age. John McNeal proposed, 40 years ago, that this BPH is characterized by an age-related reinitiation of benign neoplastic growth selectively in developmentally abortive distal ducts within the prostate transition–periurethral zone (TPZ), owing to a reawakening of inductive stroma selectively within these zones. An innovative variant of this hypothesis is that, owing to its location, the TPZ is continuously exposed to urinary components and/or autoantigens, which produces an inflammatory TPZ microenvironment that promotes recruitment of bone marrow-derived mesenchymal stem cells (MSCs) and generates a paracrine-inductive stroma that reinitiates benign neoplastic nodular growth. In support of this hypothesis, MSCs infiltrate human BPH tissue and have the ability to stimulate epithelial stem cell growth. These results provide a framework for defining both the aetiology of BPH in ageing men and insights into new therapeutic approaches.
UR - http://www.scopus.com/inward/record.url?scp=85053448903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053448903&partnerID=8YFLogxK
U2 - 10.1038/s41585-018-0087-9
DO - 10.1038/s41585-018-0087-9
M3 - Review article
C2 - 30214054
AN - SCOPUS:85053448903
VL - 15
SP - 703
EP - 715
JO - Nature Reviews Urology
JF - Nature Reviews Urology
SN - 1759-4812
IS - 11
ER -