This article explores examples of successful and unsuccessful regenerative medicine on human epithelia. To evaluate the applications of the first regenerated tissues, the analysis of the past successes and failures addresses some pending issues and lay the groundwork for developing new therapies. Research should still be encouraged to fill the gap between pathologies, clinical applications and what regenerative medicine can attain with current knowledge.

Breathing, being predominantly an automatic action, is often taken for granted. However, respiratory diseases affect millions of people globally, emerging as one of the major causes of disability and death overall. Among the respiratory dysfunctions, tracheal alterations have always represented a primary challenge for clinicians, biologists, and engineers. Indeed, in the case of wide structural alterations involving more than 50% of the tracheal length in adults or 30% in children, the available medical treatments are ineffective or inapplicable. So far, a plethora of reconstructive approaches have been proposed and clinically applied to face this growing, unmet medical need. Unfortunately, none of them has become a well-established and routinely applied clinical procedure to date. This review summarizes the main clinical reconstructive attempts and classifies them as non-tissue engineering and tissue engineering strategies. The analysis of the achievements and the main difficulties that still hinder this field, together with the evaluation of the forefront preclinical experiences in tracheal repair/replacement, is functional to promote a safer and more effective clinical translation in the near future.

No abstract

INTRODUCTION AND OBJECTIVES: The success of tissue engineering for urethral reconstruction depends on the quality of the cultures used to prepare the grafts. We investigated the quality and the safety of cultured oral and urethra mucosa cells by comparing them, in order to determine the long-term in vitro regenerative properties, the capability to maintain their differentiation program, the heterogeneity of proliferative cell pool and the differentiation potential clonogenicity.METHODS: Urethral and oral specimens were obtained in accordance with the tenets of the Declaration of Helsinki from 18 patients who underwent urethroplasty with oral mucosal graft. The primary objectives of the analysis were to determine the cell yield and migratory capacity of oral and urethral mucosa cells, to compare the protein expression, to report the clonogenicity and the long-term proliferative potential. Furthermore we characterised stem cells of urethral and oral epithelia by holoclones analysis. Finally we investigated the safety of in vitro models regard cell growth.RESULTS: A statistically significant higher cell yield was obtained from oral mucosa than from urethra (t-test p¼0,02419), but no significant differences in the number of epithelial clones. Proximity of replicative senescence boosts cell cycle (faster woundhealing capacity) in oral mucosal more than in urethra. Keratinocytes from urethral and oral mucosa underwent a mean of 79.3 and 84 cell divisions, respectively, before senescence. A similar number of holoclones, meroclones and paraclones were found in oral mucosal and urethral proliferative compartments. It is shown that a single cultured stem cell maintains 100% clonogenicity, can be identified by selected markers and can provide differentiation. Analysis of protein expression suggests maintenance of a sitespecific differentiation programme, even under culture conditions. No tumorigenicity or other abnormal cell growth developed in cultured tissues.CONCLUSIONS: The comparison of all parameters highlighted a wide similarity of the oral and urethral mucosal cells, with better wound healing via oral epithelium. The oral mucosa cells seem to have a faster wound-healing capacity and a longer replicative survival. This data might have a clinical impact regard the current longer life expectancy of our patients.INTRODUCTION AND OBJECTIVES: The cure rate of urethrotomy for urethral stricture (US) is lower than 10%. Reduction of high recurrence rates would improve patient comfort and a decrease healthcare costs. We aimed to evaluate if local injection of hADSCs could prevent fibrosis in a rat model of iatrogenic US.METHODS: After ethical approval, partial damage of the spongious urethra of male rats was created with a hypodermic needle. Then, TGFb1 (1mg) was injected into the site of urethral damage. Rats

No abstract