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.
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