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Gerald R Cunha - One of the best experts on this subject based on the ideXlab platform.
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human Urogenital Sinus mesenchyme is an inducer of prostatic epithelial development
American journal of clinical and experimental urology, 2021Co-Authors: Gerald R Cunha, Mei Cao, Amber Derpinghaus, Laurence S. BaskinAbstract:OBJECTIVE To determine whether human fetal Urogenital Sinus mesenchyme (UGM) can induce prostatic development in a responsive mouse epithelium. METHOD Male and female human fetal UGM was combined with mouse urinary bladder epithelium (BLE), and the resultant human UGM + mouse BLE tissue recombinants were grown under renal capsules of male athymic mice. Human male and female UGM was derived from reproductive tracts 9 and 14 weeks of gestation obtained following elective termination of pregnancy. At these ages prostatic ducts had already emerged from the Urogenital Sinus epithelium, and the human UGM remained contaminated with human prostatic epithelium. This unavoidable problem was tolerated because the induced mouse prostatic epithelium could be distinguished from contaminating human prostatic epithelium. RESULTS The simple columnar epithelium induced from mouse bladder epithelium by human male and female UGM resembled mouse prostatic epithelium by: (a) histology, (b) the pattern of basal cell distribution, (c) Hoechst dye nuclear staining, (d) expression of NKX3.1, (e) the pattern of androgen receptor expression and (f) the expression of probasin, a mouse prostatic secretory protein. Summary/Interpretation: These findings provide validation for mouse as a model of human prostatic development as the molecular dialogue involved in mesenchymal-epithelial interactions are sufficiently conserved that human UGM can induce mouse bladder epithelium to undergo prostatic development.
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a neuroanatomical comparison of humans and spotted hyena a natural animal model for common Urogenital Sinus clinical reflections on feminizing genitoplasty
The Journal of Urology, 2006Co-Authors: Laurence S. Baskin, Selcuk Yucel, Gerald R Cunha, Stephen E. Glickman, Ned J PlaceAbstract:Purpose: Surgical treatment of the common Urogenital Sinus phallus has been one of the most challenging areas in pediatric urology. To better understand the neuroanatomy of the common Urogenital Sinus phallus, we evaluated an animal model naturally having this condition, the spotted hyena, Crocuta crocuta. We compared the neuroanatomy of male and female humans and spotted hyenas using anatomical, immunohistochemical and 3D reconstruction techniques. We also examined the implications of the pattern of clitoral innervation for the unique challenges faced by female spotted hyenas, the only extant species of mammal that mates and gives birth through the clitoris.Materials and Methods: Three adult male and 3 female spotted hyenas were studied. With the animals under anesthesia gross anatomical examination was performed before and after artificial erection. Histological analysis was performed on one 95-day fetal male and female spotted hyena specimens, and on 18 human male and female fetal external genitalia sp...
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interactions between adult human prostatic epithelium and rat Urogenital Sinus mesenchyme in a tissue recombination model
Differentiation, 1998Co-Authors: Simon W Hayward, Peter C Haughney, Mark A Rosen, Karin M Greulich, Heinzulrich G Weier, Rajvir Dahiya, Gerald R CunhaAbstract:Tissue recombinants composed of adult human prostatic epithelium (hPrE) and rat Urogenital Sinus mesenchyme (rUGM) were grafted beneath the renal capsule of athymic rodent hosts. The pseudostratified human epithelium initially became multilayered, solid epithelial cords emerged, grew into the surrounding mesenchyme and canalized to regenerate a pseudostratified epithelium. Basal cells expressed cytokeratins 5 and 14, while luminal cells expressed cytokeratins 8 and 18, prostate specific antigen and prostatic acid phosphatase. The rat mesenchymal component differentiated into thick sheets of smooth muscle, characteristic of the human but not the rat prostate. These findings indicate that epithelial-mesenchymal interactions were reciprocal. Rat UGM induced adult hPrE to form new ductal-acinar tissue, involving epithelial proliferation, ductal branching morphogenesis and functional cytodifferentiation. Concurrently the epithelium dictated smooth muscle differentiation and patterning. Species-specific reverse transcriptase polymerase chain reaction SC (RT-PCR) analysis of the tissue recombinants was performed to separately examine the expression of epidermal growth factor (EGF), transforming growth factor-α (TGF-α), epidermal growth factor receptor (EGFR), TGF-β1, and TGF-β3 in the epithelium, stroma and host components of the graft. All of these genes, except TGF-β1, were expressed in all three tissues. Human TGF-β1 was not detected, indicating that this gene was not expressed in human prostatic epithelium but was present in stroma.
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interactions between adult human prostatic epithelium and rat Urogenital Sinus mesenchyme in a tissue recombination model
Differentiation, 1998Co-Authors: Simon W Hayward, Peter C Haughney, Mark A Rosen, Karin M Greulich, Heinzulrich G Weier, Rajvir Dahiya, Gerald R CunhaAbstract:Tissue recombinants composed of adult human prostatic epithelium (hPrE) and rat Urogenital Sinus mesenchyme (rUGM) were grafted beneath the renal capsule of athymic rodent hosts. The pseudostratified human epithelium initially became multilayered, solid epithelial cords emerged, grew into the surrounding mesenchyme and canalized to regenerate a pseudostratified epithelium. Basal cells expressed cytokeratins 5 and 14, while luminal cells expressed cytokeratins 8 and 18, prostate specific antigen and prostatic acid phosphatase. The rat mesenchymal component differentiated into thick sheets of smooth muscle, characteristic of the human but not the rat prostate. These findings indicate that epithelial-mesenchymal interactions were reciprocal. Rat UGM induced adult hPrE to form new ductal-acinar tissue, involving epithelial proliferation, ductal branching morphogenesis and functional cytodifferentiation. Concurrently the epithelium dictated smooth muscle differentiation and patterning. Species-specific reverse transcriptase polymerase chain reaction SC (RT-PCR) analysis of the tissue recombinants was performed to separately examine the expression of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGFR), TGF-beta 1, and TGF-beta 3 in the epithelium, stroma and host components of the graft. All of these genes, except TGF-beta 1, were expressed in all three tissues. Human TGF-beta 1 was not detected, indicating that this gene was not expressed in human prostatic epithelium but was present in stroma.
Wade Bushman - One of the best experts on this subject based on the ideXlab platform.
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prostate stromal and Urogenital Sinus mesenchymal cell lines for investigations of stromal epithelial interactions
Differentiation, 2008Co-Authors: Aubie Shaw, Steven Attia, Wade BushmanAbstract:Bidirectional signaling between the Urogenital Sinus epithelium and mesenchyme is an essential element of prostate development that regulates ductal morphogenesis, growth, and differentiation. Comparable interactions between the epithelium and stroma in the adult prostate appear to regulate normal growth homeostasis. Alterations in the stromal–epithelial dialogue that recapitulate features of the mesenchymal–epithelial interactions of development may play a critical role in the development of benign prostatic hyperplasia and in the progression of prostate cancer. For this reason, the mesenchymal–epithelial interactions of development are of considerable interest. In this review, we provide an overview of the mesenchymal contribution to rodent prostate development with an emphasis on the stage just before ductal budding (embryonic day 16; E16) and describe the isolation, characterization and utility of a newly established E16 Urogenital Sinus mesenchymal cell line.
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Isolation and characterization of an immortalized mouse Urogenital Sinus mesenchyme cell line.
The Prostate, 2006Co-Authors: Aubie K. Shaw, John N Papadopoulos, Curtis A. Johnson, Wade BushmanAbstract:BACKGROUND Stromal-epithelial signaling plays an important role in prostate development and cancer progression. Study of these interactions will be facilitated by the use of suitable prostate cell lines in appropriate model systems. METHODS We have isolated an immortalized prostate mesenchymal cell line from the mouse E16 Urogenital Sinus (UGS). We characterized its expression of stromal differentiation markers, response to androgen stimulation, ability to induce and participate in prostate morphogenesis, response to Shh stimulation, and interaction with prostate epithelial cells. RESULTS UGSM-2 cells express vimentin and smooth muscle actin, but not the mature smooth muscle markers myosin and desmin. This expression profile is consistent with a myofibroblast phenotype. Unlike other fibroblasts such as 3T3, UGSM-2 cells express androgen receptor mRNA and androgen stimulation increases proliferation. UGSM-2 cells are viable when grafted with embryonic UGS under the renal capsule and participate in glandular morphogenesis, but are not capable of inducing prostate morphogenesis of isolated UGS epithelium. Co-culture of UGSM-2 cells with human BPH-1 cells or co-grafting in vivo results in organized clusters of BPH-1 cells surrounded by a mantle of UGSM-2 cells. UGSM-2 cells are responsive to Sonic hedgehog (Shh), an important signaling factor in prostate development, and mimic the transcriptional response of the intact UGS mesenchyme. In co-cultures with BPH-1, UGSM-2 cells exhibit a robust transcriptional response to Shh secreted by BPH-1. CONCLUSIONS UGSM-2 is a Urogenital Sinus mesenchyme cell line that can be used to study stromal-epithelial interactions that are important in prostate biology. Prostate 66: 1347–1358, 2006. © 2006 Wiley-Liss, Inc.
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prostate development requires sonic hedgehog expressed by the Urogenital Sinus epithelium
Developmental Biology, 1999Co-Authors: Carol A Podlasek, Daniel H Barnett, J Q Clemens, P M Bak, Wade BushmanAbstract:Abstract The prostate gland develops from the Urogenital Sinus by a testosterone-dependent process of ductal morphogenesis.Sonic hedgehog(Shh) is expressed in the Urogenital Sinus epithelium and the time course of expression coincides with the formation of the main prostatic ducts. Expression is most abundant in the lumen of the Urogenital Sinus and in the contiguous proximal duct segments. The initial upregulation ofShhexpression in the male Urogenital Sinus depends on the presence of testosterone. The function of Shh was examined in the male Urogenital Sinus which was transplanted under the renal capsule of an adult male host mouse. Blockade of Shh function by a neutralizing antibody interferes with Shh signaling and abrogates growth and ductal morphogenesis in the transplanted tissue. These observations show that testosterone-dependentShhexpression in the Urogenital Sinus is necessary for the initiation of prostate development.
Laurence S. Baskin - One of the best experts on this subject based on the ideXlab platform.
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human Urogenital Sinus mesenchyme is an inducer of prostatic epithelial development
American journal of clinical and experimental urology, 2021Co-Authors: Gerald R Cunha, Mei Cao, Amber Derpinghaus, Laurence S. BaskinAbstract:OBJECTIVE To determine whether human fetal Urogenital Sinus mesenchyme (UGM) can induce prostatic development in a responsive mouse epithelium. METHOD Male and female human fetal UGM was combined with mouse urinary bladder epithelium (BLE), and the resultant human UGM + mouse BLE tissue recombinants were grown under renal capsules of male athymic mice. Human male and female UGM was derived from reproductive tracts 9 and 14 weeks of gestation obtained following elective termination of pregnancy. At these ages prostatic ducts had already emerged from the Urogenital Sinus epithelium, and the human UGM remained contaminated with human prostatic epithelium. This unavoidable problem was tolerated because the induced mouse prostatic epithelium could be distinguished from contaminating human prostatic epithelium. RESULTS The simple columnar epithelium induced from mouse bladder epithelium by human male and female UGM resembled mouse prostatic epithelium by: (a) histology, (b) the pattern of basal cell distribution, (c) Hoechst dye nuclear staining, (d) expression of NKX3.1, (e) the pattern of androgen receptor expression and (f) the expression of probasin, a mouse prostatic secretory protein. Summary/Interpretation: These findings provide validation for mouse as a model of human prostatic development as the molecular dialogue involved in mesenchymal-epithelial interactions are sufficiently conserved that human UGM can induce mouse bladder epithelium to undergo prostatic development.
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3 dimensional neuroanatomy of the human fetal pelvis anatomical support for partial Urogenital mobilization in the treatment of Urogenital Sinus
The Journal of Urology, 2008Co-Authors: Nicolas Kalfa, Mei Cao, Benchun Liu, Marcello Vilella, Michael H Hsieh, Laurence S. BaskinAbstract:Purpose: Retrospective reviews suggest that the functional outcomes of surgery of the Urogenital Sinus have often been unsatisfactory and to our knowledge the long-term results of newer surgical techniques have yet to be evaluated. A precise understanding of pelvic fetal neuroanatomy is germane for optimizing surgical correction of the Urogenital Sinus.Materials and Methods: The pelves of 10 human female fetuses were serially sectioned. Masson's trichrome staining and immunochemistry for the neuronal marker S100 (Dako Corp., Carpinteria, California) along with anatomical computer reconstruction allowed 3-dimensional analysis of the nerves in relation to the pelvic structures as an animated motion picture.Results: Two types of neuronal structures were identified. 1) A dense perivisceral foil of branching nerves closely surrounded the pelvic organs. The localization of most nerves was on the external faces of the viscera with a limited fraction in the rectovaginal and urethrovaginal septa. This innervation ...
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a neuroanatomical comparison of humans and spotted hyena a natural animal model for common Urogenital Sinus clinical reflections on feminizing genitoplasty
The Journal of Urology, 2006Co-Authors: Laurence S. Baskin, Selcuk Yucel, Gerald R Cunha, Stephen E. Glickman, Ned J PlaceAbstract:Purpose: Surgical treatment of the common Urogenital Sinus phallus has been one of the most challenging areas in pediatric urology. To better understand the neuroanatomy of the common Urogenital Sinus phallus, we evaluated an animal model naturally having this condition, the spotted hyena, Crocuta crocuta. We compared the neuroanatomy of male and female humans and spotted hyenas using anatomical, immunohistochemical and 3D reconstruction techniques. We also examined the implications of the pattern of clitoral innervation for the unique challenges faced by female spotted hyenas, the only extant species of mammal that mates and gives birth through the clitoris.Materials and Methods: Three adult male and 3 female spotted hyenas were studied. With the animals under anesthesia gross anatomical examination was performed before and after artificial erection. Histological analysis was performed on one 95-day fetal male and female spotted hyena specimens, and on 18 human male and female fetal external genitalia sp...
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the impact of prenatal androgens on vaginal and Urogenital Sinus development in the female mouse
The Journal of Urology, 2004Co-Authors: Selcuk Yucel, Andre G Cavalcanti, Zhong Wang, Laurence S. BaskinAbstract:ABSTRACTPurpose: In females abnormal Urogenital virilization can occur secondary to prenatal exposure to exogenous or endogenous androgens. We studied the effects of different doses of prenatal androgens on Urogenital Sinus development and the location of the vaginal confluence in a mouse model.Materials and Methods: Timed pregnant C57/6 mice were exposed to 2, 5 and 10 mg testosterone propionate on gestational days 14 through 18. On gestational day 19 the genital tubercles and internal genitalia were examined grossly and histologically for the presence of virilization. Three-dimensional computer reconstruction was done and plastic cast injection molds of the Urogenital Sinus were made in select specimens.Results: Microscopic analysis confirmed the spectrum of virilization, which occurred in 98% of testosterone propionate treated female fetuses. Plastic cast injection showed that affected females had a longer Urogenital Sinus, more proximal confluence and shorter vagina in a dose dependent manner. Histolo...
Simon W Hayward - One of the best experts on this subject based on the ideXlab platform.
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interactions between adult human prostatic epithelium and rat Urogenital Sinus mesenchyme in a tissue recombination model
Differentiation, 1998Co-Authors: Simon W Hayward, Peter C Haughney, Mark A Rosen, Karin M Greulich, Heinzulrich G Weier, Rajvir Dahiya, Gerald R CunhaAbstract:Tissue recombinants composed of adult human prostatic epithelium (hPrE) and rat Urogenital Sinus mesenchyme (rUGM) were grafted beneath the renal capsule of athymic rodent hosts. The pseudostratified human epithelium initially became multilayered, solid epithelial cords emerged, grew into the surrounding mesenchyme and canalized to regenerate a pseudostratified epithelium. Basal cells expressed cytokeratins 5 and 14, while luminal cells expressed cytokeratins 8 and 18, prostate specific antigen and prostatic acid phosphatase. The rat mesenchymal component differentiated into thick sheets of smooth muscle, characteristic of the human but not the rat prostate. These findings indicate that epithelial-mesenchymal interactions were reciprocal. Rat UGM induced adult hPrE to form new ductal-acinar tissue, involving epithelial proliferation, ductal branching morphogenesis and functional cytodifferentiation. Concurrently the epithelium dictated smooth muscle differentiation and patterning. Species-specific reverse transcriptase polymerase chain reaction SC (RT-PCR) analysis of the tissue recombinants was performed to separately examine the expression of epidermal growth factor (EGF), transforming growth factor-α (TGF-α), epidermal growth factor receptor (EGFR), TGF-β1, and TGF-β3 in the epithelium, stroma and host components of the graft. All of these genes, except TGF-β1, were expressed in all three tissues. Human TGF-β1 was not detected, indicating that this gene was not expressed in human prostatic epithelium but was present in stroma.
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interactions between adult human prostatic epithelium and rat Urogenital Sinus mesenchyme in a tissue recombination model
Differentiation, 1998Co-Authors: Simon W Hayward, Peter C Haughney, Mark A Rosen, Karin M Greulich, Heinzulrich G Weier, Rajvir Dahiya, Gerald R CunhaAbstract:Tissue recombinants composed of adult human prostatic epithelium (hPrE) and rat Urogenital Sinus mesenchyme (rUGM) were grafted beneath the renal capsule of athymic rodent hosts. The pseudostratified human epithelium initially became multilayered, solid epithelial cords emerged, grew into the surrounding mesenchyme and canalized to regenerate a pseudostratified epithelium. Basal cells expressed cytokeratins 5 and 14, while luminal cells expressed cytokeratins 8 and 18, prostate specific antigen and prostatic acid phosphatase. The rat mesenchymal component differentiated into thick sheets of smooth muscle, characteristic of the human but not the rat prostate. These findings indicate that epithelial-mesenchymal interactions were reciprocal. Rat UGM induced adult hPrE to form new ductal-acinar tissue, involving epithelial proliferation, ductal branching morphogenesis and functional cytodifferentiation. Concurrently the epithelium dictated smooth muscle differentiation and patterning. Species-specific reverse transcriptase polymerase chain reaction SC (RT-PCR) analysis of the tissue recombinants was performed to separately examine the expression of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGFR), TGF-beta 1, and TGF-beta 3 in the epithelium, stroma and host components of the graft. All of these genes, except TGF-beta 1, were expressed in all three tissues. Human TGF-beta 1 was not detected, indicating that this gene was not expressed in human prostatic epithelium but was present in stroma.
Owen N Witte - One of the best experts on this subject based on the ideXlab platform.
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preparation of Urogenital Sinus mesenchymal cells for prostate tissue recombination models
CSH Protocols, 2015Co-Authors: Yang Zong, Andrew S Goldstein, Owen N WitteAbstract:An appropriate microenvironment provided by the mesenchyme is important for establishing tissue recombination models for epithelial cancer. Urogenital Sinus mesenchymal (UGSM) cells derived from embryonic rodent show potent inductive effects for prostate regeneration. Genetic manipulation of these mesenchymal cells allows us to define the contribution of the tumor microenvironment to prostate cancer development. This protocol describes preparation and propagation of murine UGSM cells in culture.
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in vivo regeneration of murine prostate from dissociated cell populations of postnatal epithelia and Urogenital Sinus mesenchyme
Proceedings of the National Academy of Sciences of the United States of America, 2003Co-Authors: Li Xin, Hisamitsu Ide, Yoon Ki Kim, Purnima Dubey, Owen N WitteAbstract:The existence of a postnatal prostate stem cell is supported by several types of evidence. Withdrawal of androgen leads to involution of the gland, but readdition can rapidly stimulate regeneration. Tissue fragments derived from mouse or rat prostatic epithelia from midgestation embryos or adult mice, when combined with tissue fragments from Urogenital Sinus mesenchyme and grafted under the kidney capsule, can regenerate prostatic structures. Indirect evidence supports that the stem cell population is contained within the basal layer. Purified prostatic stem cell preparations would be useful to define the physical and functional properties required for regeneration and to compare with cells that accumulate during abnormal growth states, like prostate cancer. We have developed a regeneration system using dissociated cell populations of postnatal prostate epithelia and embryonic Urogenital Sinus mesenchyme. Efficient in vivo regeneration of prostatic structures in the subcapsular space of the kidney was observed within 4-8 wk with as few as 103 epithelial cells from prostates derived from donors 10 d to 6 wk of age. The regenerated structures show a branching tubular epithelial morphology, with expression of a panel of markers consistent with prostate development. Donor epithelial populations can be readily infected with GFP expressing lentiviral vectors to provide integration markers and easy visualization. The cell preparations of Urogenital Sinus mesenchyme can be expanded in short-term in vitro culture while their inductive capabilities are retained. Further definition of the subpopulation of prostate epithelial cells containing the regeneration activity should be possible with such technologies.
