ABSTRACT
BACKGROUND@#The urinary tract can be affected by both congenital abnormalities as well as acquired disorders, such ascancer, trauma, infection, inflammation, and iatrogenic injuries, all of which may lead to organ damage requiring eventualreconstruction. As a gold standard, gastrointestinal segment is used for urinary bladder reconstruction. However, one majorproblem is that while bladder tissue prevents reabsorption of specific solutes, gastrointestinal tissue actually absorbs them.Therefore, tissue engineering approach had been attempted to provide an alternative tissue graft for urinary bladderreconstruction. @*METHODS@#Human adipose-derived stem cells isolated from fat tissues were differentiated into smooth muscle cells andthen seeded onto a triple-layered PLGA sheet to form a bladder construct. Adult athymic rats underwent subtotal urinarybladder resection and were divided into three treatment groups (n = 3): Group 1 (‘‘sham’’) underwent anastomosis of theremaining basal region, Group 2 underwent reconstruction with the cell-free scaffold, and Group 3 underwent reconstructionwith the tissue-engineered bladder construct. Animals were monitored on a daily basis and euthanisation wasperformed whenever a decline in animal health was detected. @*RESULTS@#All animals in Groups 1, 2 and 3 survived for at least 7 days and were followed up to a maximum of 12 weekspost-operation. It was found that by Day 14, substantial ingrowth of smooth muscle and urothelial cells had occurred inGroup 2 and 3. In the long-term follow up of group 3 (tissue-engineered bladder construct group), it was found that theurinary bladder wall was completely regenerated and bladder function was fully restored. Urodynamic and radiologicalevaluations of the reconstructed bladder showed a return to normal bladder volume and function.Histological analysisrevealed the presence of three muscular layers and a urothelium similar to that of a normal bladder. Immunohistochemicalstaining using human-specific myocyte markers (myosin heavy chain and smoothelin) confirmed the incorporation of theseeded cells in the newly regenerated muscular layers. @*CONCLUSION@#Implantation of PLGA construct seeded with smooth muscle cells derived from human adipose stemcells can lead to regeneration of the muscular layers and urothelial ingrowth, leading to formation of a completelyfunctional urinary bladder.
ABSTRACT
BACKGROUND@#The urinary tract can be affected by both congenital abnormalities as well as acquired disorders, such ascancer, trauma, infection, inflammation, and iatrogenic injuries, all of which may lead to organ damage requiring eventualreconstruction. As a gold standard, gastrointestinal segment is used for urinary bladder reconstruction. However, one majorproblem is that while bladder tissue prevents reabsorption of specific solutes, gastrointestinal tissue actually absorbs them.Therefore, tissue engineering approach had been attempted to provide an alternative tissue graft for urinary bladderreconstruction. @*METHODS@#Human adipose-derived stem cells isolated from fat tissues were differentiated into smooth muscle cells andthen seeded onto a triple-layered PLGA sheet to form a bladder construct. Adult athymic rats underwent subtotal urinarybladder resection and were divided into three treatment groups (n = 3): Group 1 (‘‘sham’’) underwent anastomosis of theremaining basal region, Group 2 underwent reconstruction with the cell-free scaffold, and Group 3 underwent reconstructionwith the tissue-engineered bladder construct. Animals were monitored on a daily basis and euthanisation wasperformed whenever a decline in animal health was detected. @*RESULTS@#All animals in Groups 1, 2 and 3 survived for at least 7 days and were followed up to a maximum of 12 weekspost-operation. It was found that by Day 14, substantial ingrowth of smooth muscle and urothelial cells had occurred inGroup 2 and 3. In the long-term follow up of group 3 (tissue-engineered bladder construct group), it was found that theurinary bladder wall was completely regenerated and bladder function was fully restored. Urodynamic and radiologicalevaluations of the reconstructed bladder showed a return to normal bladder volume and function.Histological analysisrevealed the presence of three muscular layers and a urothelium similar to that of a normal bladder. Immunohistochemicalstaining using human-specific myocyte markers (myosin heavy chain and smoothelin) confirmed the incorporation of theseeded cells in the newly regenerated muscular layers. @*CONCLUSION@#Implantation of PLGA construct seeded with smooth muscle cells derived from human adipose stemcells can lead to regeneration of the muscular layers and urothelial ingrowth, leading to formation of a completelyfunctional urinary bladder.
ABSTRACT
BACKGROUND: Urinary tract is subjected to a variety of disorders such as urethral stricture, which often develops as a result of scarring process. Urethral stricture can be treated by urethral dilation and urethrotomy; but in cases of long urethral strictures, substitution urethroplasty with genital skin and buccal mucosa grafts is the only option. However a number of complications such as infection as a result of hair growth in neo-urethra, and stone formation restrict the application of those grafts. Therefore, tissue engineering techniques recently emerged as an alternative approach, aiming to overcome those restrictions. The aim of this review is to provide a comprehensive coverage on the strategies employed and the translational status of urethral tissue engineering over the past years and to propose a combinatory strategy for the future of urethral tissue engineering. METHODS: Data collection was based on the key articles published in English language in years between 2006 and 2018 using the searching terms of urethral stricture and tissue engineering on PubMed database. RESULTS: Differentiation of mesenchymal stem cells into urothelial and smooth muscle cells to be used for urologic application does not offer any advantage over autologous urothelial and smooth muscle cells. Among studied scaffolds, synthetic scaffolds with proper porosity and mechanical strength is the best option to be used for urethral tissue engineering. CONCLUSION: Hypoxia-preconditioned mesenchymal stem cells in combination with autologous cells seeded on a prevascularized synthetic and biodegradable scaffold can be said to be the best combinatory strategy in engineering of human urethra.