Molecular, cellular and developmental biology of urothelium as a basis of bladder regeneration

Staack, Andrea; Hayward, Simon W.; Baskin, Laurence S.; Cunha, Gerald R.

doi:10.1111/j.1432-0436.2005.00014.x

Cited by 78 publications

(50 citation statements)

References 99 publications

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“…Improving our knowledge in this regard is vital to support medical efforts in bladder reconstruction. In fact, current bladder reconstruction approaches often utilize other endodermal organs, such as the ileum and the colon as the source of autograft tissue to construct bladderlike reservoirs (Staack et al, 2005). Although the development of these endodermally derived tissues was also influenced by Shh, the ultimate structure and physiological character of mature gut and bladder are obviously significantly different.…”

Section: Research Articlementioning

confidence: 99%

“…Although the development of these endodermally derived tissues was also influenced by Shh, the ultimate structure and physiological character of mature gut and bladder are obviously significantly different. Hence, multiple complications, including electrolyte imbalance and stone formation were observed after the use of gastrointestinal mucosa or mesenchyme for bladder repair (Staack et al, 2005). Therefore, elucidation of the developmental mechanisms driving embryonic mesenchyme toward functional bladder tissues is likely to have significant impact when translated to the medical arena.…”

Section: Research Articlementioning

confidence: 99%

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Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling

Haraguchi

Motoyama

Sasaki³

et al. 2007

Development

137

162

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The urogenital and reproductive organs, including the external genitalia, bladder and urethra, develop as anatomically aligned organs. Descriptive and experimental embryology suggest that the cloaca, and its derivative, the urogenital sinus, contribute to the formation of these organs. However, it is unknown how the primary tissue lineages in, and adjacent to, the cloaca give rise to the above organs, nor is bladder formation understood. While it is known that sonic hedgehog (Shh) is expressed by the cloacal epithelia, the developmental programs that regulate and coordinate the formation of the urogenital and reproductive organs have not been elucidated. Here we report that Shh mutant embryos display hypoplasia of external genitalia, internal urethra (pelvic urethra) and bladder. The importance of Shh signaling in the development of bladder and external genitalia was confirmed by analyzing a variety of mutant mouse lines with defective hedgehog signaling. By genetically labeling hedgehog-responding tissue lineages adjacent to the cloaca and urogenital sinus, we defined the contribution of these tissues to the bladder and external genitalia. We discovered that development of smooth muscle myosin-positive embryonic bladder mesenchyme requires Shh signaling, and that the bladder mesenchyme and dorsal (upper) external genitalia derive from Shh-responsive peri-cloacal mesenchyme. Thus, the mesenchymal precursors for multiple urogenital structures derive from peri-cloacal mesenchyme and the coordination of urogenital organ formation from these precursors is orchestrated by Shh signals.

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Section: Research Articlementioning

confidence: 99%

Section: Research Articlementioning

confidence: 99%

Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling

Haraguchi

Motoyama

Sasaki³

et al. 2007

Development

137

162

View full text Add to dashboard Cite

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“…Immunoblotting confirmed that the in vivo ureteral urothelium contains much fewer uroplakins (ϳ10-fold lower on a per milligram cellular protein basis) than bladder urothelium. To see whether such phenotypic differences can be explained by different mesenchymal signals (extrinsic modulation of epithelial differentiation) (14,91), we compared the in vitro growth and differentiation of cultured bovine ureter, bladder, and bladder neck/proximal urethral urothelial cells after they had been serially expanded in an identical environment (with 3T3 feeder cells) to "dilute out" any residual mesenchymal signals that might have been present in the in vivo urothelium. The observation that cultured ureteral and bladder urothelial cells remain distinct in their morphology (Fig.…”

Section: Urothelial Heterogeneity and Its Implications For Cultured Umentioning

confidence: 99%

“…1, B and C). These plaques are thought to play an important role in reversibly adjusting the apical surface area, stabilizing and preventing the apical urothelial surface from rupturing during bladder distention, and forming one of the most effective permeability barriers existing in nature (2,38,53,66,91,96).…”

mentioning

confidence: 99%

Altered phenotype of cultured urothelial and other stratified epithelial cells: implications for wound healing

Sun¹

2006

American Journal of Physiology-Renal Physiology

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Sun, Tung-Tien. Altered phenotype of cultured urothelial and other stratified epithelial cells: implications for wound healing. Am J Physiol Renal Physiol 291: F9 -F21, 2006; doi:10.1152/ajprenal.00035.2006.-The differentiation of cultured stratified epithelial cells can deviate significantly from that of normal epithelium, leading to suggestions that cultured cells undergo abnormal differentiation, or a truncated differentiation. Thus cultured epidermal and corneal epithelial cells stop synthesizing their tissue-specific keratin pair K1/K10 and K3/K12, respectively. The replacement of these keratins in the suprabasal compartment by K6/K16 keratins that are made by all stratified squamous epithelia during hyperplasia rules out a truncated differentiation. Importantly, the keratin pattern of in vivo corneal epithelium undergoing wound repair mimics that of cultured rabbit corneal epithelial cells. Although cultured urothelial cells continue to synthesize uroplakins, which normally form two-dimensional crystalline urothelial plaques covering almost the entire apical urothelial surface, these proteins do not assemble into crystals in cultured cells. Cultured epithelial cells can, however, rapidly regain normal differentiation on the removal of mitogenic stimuli, the use of a suitable extracellular matrix, or the transplantation of the cells to an in vivo, nonmitogenic environment. These data suggest that cultured epithelial cells adopt altered differentiation patterns mimicking in vivo regenerating or hyperplastic epithelia. Blocking the synthesis of tissue-specific differentiation products, such as the K1 and K10 keratins designed to form extensive disulfide cross-links in cornified cells, or the assembly of uroplakin plaques allows epithelial cells to better migrate and proliferate, activities that are of overriding importance during wound repair. Cultured urothelial and other stratified epithelial cells provide excellent models for studying the regulation of the synthesis and assembly of differentiation products, a key cellular process during epithelial wound repair. bladder epithelium; uroplakin; urothelial plaque; permeability barrier THE ABILITY TO GROW CELLS of stratified squamous epithelia and to reproduce their in vivo differentiation program under welldefined in vitro conditions can greatly facilitate the study of the growth and differentiation of these cell types. Thus the in vitro cultivation of human epidermal cells using lethally irradiated or mitomycin-treated 3T3 feeder cells (80) made possible early breakthroughs in studying the synthesis of keratins (23,24,97,98) and the formation of cornified envelope (83,84,95), and for using in vitro expanded epidermal cells to treat burn patients (21,25). Studies of the differentiation of cultured corneal epithelial cells led to the discovery that corneal epithelial stem cells reside in the basal cell layer of peripheral corneal epithelium in a previously ignored area called the limbus (87) and to the use of cultured corneal epithelial cells in restoring patie...

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“…These paracrine-signaling events orchestrate the development and functions of organs establishing morphology during organogenesis and maintaining adult differentiation. Previous studies have demonstrated that cellcell signaling between the stroma and epithelium are integral for correct bladder development (Baskin et al, 1996a(Baskin et al, ,b, 2001DiSandro et al, 1998;Liu et al, 2000;Staack et al, 2005). Studies by Baskin and co-workers have demonstrated reciprocal cellcell signaling between the stromal and epithelial compartments.…”

Section: Introductionmentioning

confidence: 98%

Bladder tissue formation from cultured bladder urothelium

Oottamasathien

Williams

Franco

et al. 2006

Developmental Dynamics

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Tissue recombination is a powerful method to evaluate the paracrine-signaling events that orchestrate the development of organs using the in vivo environment of a host rodent. Studies have reported the successful generation of primary cultures of rodent bladder urothelium, but none have reported their use to recapitulate bladder tissue with tissue recombination. We propose that primary cultured bladder urothelium, when recombined with inductive embryonic bladder mesenchyme, will form bladder tissue in a recombination model. Adult rat bladders were isolated and urothelium obtained. Sheets of bladder urothelium were re-suspended in collagen and maintained in tissue culture. After expansion (>20 passages), the urothelium was recombined with embryonic day-14 mouse bladder mesenchyme, then grafted beneath the renal capsule of immunocompromised mouse hosts. Grafts were harvested after 28 days. Control grafts were performed with bladder mesenchyme alone, cultured bladder urothelium alone, and collagen matrix alone. Final tissues were evaluated with staining and immunohistochemistry (H&E, Gomori's trichrome, broad-spectrum uroplakin, and smooth muscle actin ␣ and ␥). Immunocytochemistry on cultured urothelium for broad-spectrum keratin, vimentin, and broad-spectrum uroplakin confirmed pure populations, void of mesenchymal contaminants. Staining of recombinant grafts demonstrated bladder tissue with mature urothelium and stromal differentiation. Control tissues were void of bladder tissue formation. We have successfully demonstrated that a chimeric bladder is formed from primary cultured bladder urothelium recombined with embryonic bladder mesenchyme. This is a powerful new tool for investigating the molecular mechanisms of bladder development and disease. Future applications may include the in vitro genetic manipulation of urothelium and examining those effects on growth and development in an in vivo environment. Developmental Dynamics 235:2795-2801, 2006.

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Molecular, cellular and developmental biology of urothelium as a basis of bladder regeneration

Cited by 78 publications

References 99 publications

Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling

Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling

Altered phenotype of cultured urothelial and other stratified epithelial cells: implications for wound healing

Bladder tissue formation from cultured bladder urothelium

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