The intrinsic ability to display self-organizing morphogenetic properties in ex vivo culture may represent a general property of tissue stem cells. Here we show that single luminal stem/progenitor cells can generate prostate organoids in a three-dimensional culture system in the absence of stroma. Organoids generated from CARNs (castration-resistant Nkx3.1-expressing cells) or normal prostate epithelium exhibit tissue architecture containing luminal and basal cells, undergo long-term expansion in culture, and display functional androgen receptor signaling. Lineage-tracing demonstrates that luminal cells are favored for organoid formation, and generate basal cells in culture. Furthermore, tumor organoids can initiate from CARNs after oncogenic transformation, and from mouse models of prostate cancer, and can facilitate analyses of drug response. Finally, we provide evidence supporting the feasibility of organoid studies of human prostate tissue. Our studies underscore the progenitor properties of luminal cells, and identify in vitro approaches for studying prostate biology.

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Objective To phenotypically characterize ADAMTS‐4– and ADAMTS‐5–double‐knockout mice, and to determine the effect of deletion of ADAMTS‐4 and ADAMTS‐5 on the progression of osteoarthritis (OA) in mice. Methods Mice lacking the catalytic domain of ADAMTS‐4 and ADAMTS‐5 were crossed to generate ADAMTS‐4/5–double‐knockout animals. Twelve‐week‐old and 1‐year‐old male and female ADAMTS‐4/5–double‐knockout mice were compared with age‐ and sex‐matched wild‐type (WT) mice by evaluating terminal body weights, organ weights, clinical pathology parameters, PIXImus mouse densitometry findings, and macroscopic and microscopic observations. ADAMTS‐4/5–double‐knockout mice were challenged by surgical induction of joint instability to determine the importance of these genes in the progression of OA. Articular and nonarticular cartilage explants from WT and ADAMTS‐4/5–double‐knockout mice were treated with interleukin‐1 (IL‐1) plus retinoic acid ex vivo, to examine proteoglycan degradation. Results There were no genotype‐related phenotype differences between ADAMTS‐4/5–double‐knockout and WT mice through 1 year of age, with the exception that female ADAMTS‐4/5–double‐knockout mice had a lower mean terminal body weight at the 12‐week time point. Eight weeks after surgical induction of joint instability, OA was significantly less severe in ADAMTS‐4/5–double‐knockout mice compared with WT mice. Following stimulation of cartilage explants with IL‐1 plus retinoic acid, aggrecanase‐mediated degradation in ADAMTS‐4/5–double‐knockout mice was ablated, to a level comparable with that in ADAMTS‐5–knockout mice. Conclusion Dual deletion of ADAMTS‐4 and ADAMTS‐5 generated mice that were phenotypically indistinguishable from WT mice. Deletion of ADAMTS‐4/5 provided significant protection against proteoglycan degradation ex vivo and decreased the severity of murine OA. These effects in the ADAMTS‐4/5–double‐knockout mice were comparable with those observed with deletion of ADAMTS‐5 alone.

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OBJECTIVESTo report updated results, at 1 year of followup, of a modified nerve-sparing robotic radical prostatectomy that preserves the lateral prostatic fascia (Veil of Aphrodite). PATIENTS AND METHODSFrom January to December 2003, 154 consecutive men had a Vattikuti Institute prostatectomy with Veil of Aphrodite nervesparing by one surgeon. A prospective database recorded patient demographics, intraoperative, peri-operative, and pathological variables. Peri-operative complications were recorded using the Clavien classification. Patients had serum prostate-specific antigen (PSA) levels measured every 3 months and selfadministered the International Prostate Symptom Score and Sexual Health Inventory for Male questionnaires before and at 1 year after surgery. RESULTSThe men had a mean age of 57.4 years, a mean body mass index of 27.2 kg/m 2 , and a mean PSA level before surgery of 5.11 ng/mL. The mean operative duration was 122 min. At 1 year, 96% of the men reported having had intercourse and 71% had recovered normal erectile function. One man had a Clavien grade II complication, 4.6% of men with organ-confined disease had positive surgical margins, and no patient had a PSA recurrence at 12 months; 97% of the men were continent at 1 year, and the median time to continence was 14 days.