Tissue Eng Regen Med.  2020 Aug;17(4):553-563. 10.1007/s13770-020-00271-7.

Incorporation of Smooth Muscle Cells Derived from HumanAdipose Stem Cells on Poly(Lactic-co-Glycolic Acid) Scaffoldfor the Reconstruction of Subtotally Resected Urinary Bladderin Athymic Rats

• Salem SA
• Rashidbenam Z
• Jasman MH
• Ho CCK
• Sagap I
• Singh R
• Yusof MR
• Zainuddin ZM
• Idrus RBH
• Ng MH

• KMID: 2505182
• DOI: http://doi.org/10.1007/s13770-020-00271-7

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.

Keyword

Bladder reconstruction; PLGA; Adipose-dervied stem cells; Tissue engineering; Smooth muscle cells