Collagen cell carriers seeded with human urothelial cells for urethral reconstructive surgery: first results in a xenograft minipig model.

PURPOSE: Urethral strictures are a common disease of the lower urinary tract in men. At present, the use of buccal mucosa is the method of choice for long or recurrent strictures. However, autologous tissue-engineered grafts are still under investigation for reconstructive urological surgery. The aim of this pilot study was to evaluate the use of human urothelial cells (HUC) seeded on bovine collagen type I-based cell carriers (CCC) in an animal model and to evaluate short-term outcome of the surgical procedure. METHODS: Four male Göttingen minipigs were used with immunosuppression (cyclosporine A) for this pilot xenograft study. HUC obtained from human benign ureteral tissue were stained by PKH26 and seeded on a collagen cell carrier (CCC). Seven weeks after urethral stricture induction and protective vesicostomy, cell-seeded CCC was implanted in the urethra with HUC luminal and antiluminal, respectively. After two weeks animals were euthanized, urethrography and histological assessment were performed. RESULTS: Surgery was technically feasible in all minipigs. Stricture was radiologically established 7 weeks after induction. CCC was visible after two weeks and showed good integration without signs of inflammation or rejection. In the final urethrography, no remaining stricture could be detected. Near porcine urothelium, PKH26-positive areas were found even if partially detached from CCC. Although diminished, immunofluorescence with pankeratin, CK20, E-cadherin and ZO-1 showed intact urothelium in several areas on and nearby CCC. CONCLUSION: Finally, this study demonstrates that the HUC-seeded CCC used as a xenograft in minipigs is technically feasible and shows promising results for further studies.

Cell-based therapy for the deficient urinary sphincter.

When sterile culture techniques of mammalian cells first became state of the art, there was tremendous anticipation that such cells could be eventually applied for therapeutic purposes. The discovery of adult human stem or progenitor cells further motivated scientists to pursue research in cell-based therapies. Although evidence from animal studies suggests that application of cells yields measurable benefits, in urology and many other disciplines, progenitor-cell-based therapies are not yet routinely clinically available. Stress urinary incontinence (SUI) is a condition affecting a large number of patients. The etiology of SUI includes, but is not limited to, degeneration of the urinary sphincter muscle tissue and loss of innervation, as well as anatomical and biomechanical causes. Therefore, different regimens were developed to treat SUI. However, at present, a curative functional treatment is not at hand. A progenitor-cell-based therapy that can tackle the etiology of incontinence, rather than the consequences, is a promising strategy. Therefore, several research teams have intensified their efforts to develop such a therapy for incontinence. Here, we introduce candidate stem and progenitor cells suitable for SUI treatment, show how the functional homogeneity and state of maturity of differentiated cells crucial for proper tissue integration can be assessed electrophysiologically prior to their clinical application, and discuss the trophic potential of adult mesenchymal stromal (or stem) cells in regeneration of neuronal function.

Blueberry muffin rash secondary to hereditary spherocytosis.

The term blueberry muffin rash is used to describe the clinical presentation of dermal extramedullary hematopoiesis. The common culprits of this rash include a TORCH (toxoplasmosis, other agents, rubella, cytomegalovirus, herpes) infection or hematologic dyscrasia. Association of this rash with hereditary spherocytosis is extremely rare. We present a unique case of a neonate born with a blueberry muffin rash secondary to hereditary spherocytosis.

Patient Knowledge and Qualities of Treatment Decisions for Localized Prostate Cancer.

BACKGROUND: Controversy surrounds treatment for localized prostate cancer (LPC). OBJECTIVES: To assess men's localized prostate cancer (LPC) knowledge and its association with decision-making difficulty, satisfaction and regret. METHODS: Population-based sample of 201 men (104 white, 97 black), ≤ 75 years with newly diagnosed LPC completed a self-administered survey. RESULTS: Mean age was 61(±7.6) years; two-thirds had less than a Bachelor's degree. Mean LPC knowledge was low, 5.87 (±2.53, maximum score 11). More than a third of men who received surgery or radiation did not know about serious long-term treatment side effects. Fewer than half of the men correctly answered comparative side effect and survival benefit questions between surgery and radiation. Knowledge gaps were greatest among black men, men with lower education, single men. Tumor aggressiveness (i.e. PSA level, Gleason score) and treatment choice were not associated with knowledge. Knowledge was not associated with decisional satisfaction or regret. However, greater knowledge was associated with greater decision-making difficulty (P = .018). CONCLUSIONS: Significant LPC knowledge gaps existed across groups, with greater knowledge gaps among black men. The association of decision-making difficulty with knowledge was independent of race. Better patient education is needed, but may not alleviate men's decision-making difficulty due to inherent scientific uncertainty.

Stem cell therapy for voiding and erectile dysfunction.

Voiding dysfunction comprises a variety of disorders, including stress urinary incontinence and overactive bladder, and affects millions of men and women worldwide. Erectile dysfunction (ED) also decreases quality of life for millions of men, as well as for their partners. Advanced age and diabetes are common comorbidities that can exacerbate and negatively impact upon the development of these disorders. Therapies that target the pathophysiology of these conditions to halt progression are not currently available. However, stem cell therapy could fill this therapeutic void. Stem cells can reduce inflammation, prevent fibrosis, promote angiogenesis, recruit endogenous progenitor cells, and differentiate to replace damaged cells. Adult multipotent stem cell therapy, in particular, has shown promise in case reports and preclinical animal studies. Stem cells also have a role in urological tissue engineering for ex vivo construction of bladder wall and urethral tissue (using a patient's own cells) prior to transplantation. More recent studies have focused on bioactive factor secretion and homing of stem cells. In the future, clinicians are likely to utilize allogeneic stem cell sources, intravenous systemic delivery, and ex vivo cell enhancement to treat voiding dysfunction and ED.

From tissue engineering to regenerative medicine in urology--the potential and the pitfalls.

Tissue engineering is a promising technique for the development of biological substitutes that can restore, maintain, or improve tissue function. The creation of human tissue-engineered products, generated of autologous somatic cells or adult stem cells with or without seeding of biocompatible matrices is a vision to resolve the lack of tissues and organs for transplantation and to offer new options for reconstructive surgery. Tissue engineering in urology aims at the reconstruction of the urinary tract by creating anatomically and functionally equal tissue. It is a rapidly evolving field in basic research and the transfer into the clinic has yet to be realized. Necessary steps from bench to bed are the proof of principle in animal models and the proof of concept in clinical trials following good manufacturing practice and ethical and legal requirements for human tissue-engineered products. Up to now, obstacles still occur in the neovascularization of implants and ingrowth of nerves in vivo. Moreover the harvesting of mesenchymal stem cells out of bone marrow as well as the explant of urothelial cells yet demands rather invasive surgery to achieve a successful outcome. Thus, other cell sources and harvesting techniques like placenta and adipose tissue for mesenchymal stem cells and bladder irrigation for urothelial cells require closer investigation.