Optimization of the current self-assembled urinary bladder model: Organ-specific stroma and smooth muscle inclusion
DOI:
https://doi.org/10.5489/cuaj.2953Keywords:
urinary bladder, urothelium, in vitro model, tissue engineering, urethroplasty, bladder augmentationAbstract
Introduction: Due to the complications associated with the use of non-native biomaterials and the lack of local tissues, bioengineered tissues are required for surgical reconstruction of complex urinary tract diseases, including those of the urinary bladder. The selfassembly method of matrix formation using autologous stromal cells obviates the need for exogenous biomaterials. We aimed at creating novel ex-vivo multilayer urinary tissue from a single bladder biopsy.
Methods: After isolating urothelial, bladder stromal and smooth muscle cells from bladder biopsies, we produced 2 models of urinary equivalents: (1) the original one with dermal fibroblasts and (2) the new one with bladder stromal cells. Dermal fibroblasts and bladder stromal cells were stimulated to form an extracellular matrix, followed by sequential seeding of smooth muscle cells and urothelial cells. Stratification and cellular differentiation were assessed by histology, immunostaining and electron microscopy. Barrier function was checked with the permeability test. Biomechanical properties were assessed with uniaxinal tensile strength, elastic modulus, and failure strain.
Results: Both urinary equivalents could be handled easily and did not contract. Stratified epithelium, intact basement membrane, fused matrix, and prominent muscle layer were detected in both urinary equivalents. Bladder stromal cell-based constructs had terminally differentiated urothelium and more elasticity than dermal fibroblasts-based equivalents. Permeation studies showed that both equivalents were comparable to native tissues.
Conclusions: Organ-specific stromal cells produced urinary tissues with more terminally differentiated urothelium and better biomechanical characteristics than non-specific stromal cells. Smooth muscle cells could be incorporated into the selfassembled tissues effectively. This multi-layer tissue can be used as a urethral graft or as a bladder model for disease modelling and pharmacotherapeutic testing.
Downloads
Downloads
Published
How to Cite
Issue
Section
License
You, the Author(s), assign your copyright in and to the Article to the Canadian Urological Association. This means that you may not, without the prior written permission of the CUA:
- Post the Article on any Web site
- Translate or authorize a translation of the Article
- Copy or otherwise reproduce the Article, in any format, beyond what is permitted under Canadian copyright law, or authorize others to do so
- Copy or otherwise reproduce portions of the Article, including tables and figures, beyond what is permitted under Canadian copyright law, or authorize others to do so.
The CUA encourages use for non-commercial educational purposes and will not unreasonably deny any such permission request.
You retain your moral rights in and to the Article. This means that the CUA may not assert its copyright in such a way that would negatively reflect on your reputation or your right to be associated with the Article.
The CUA also requires you to warrant the following:
- That you are the Author(s) and sole owner(s), that the Article is original and unpublished and that you have not previously assigned copyright or granted a licence to any other third party;
- That all individuals who have made a substantive contribution to the article are acknowledged;
- That the Article does not infringe any proprietary right of any third party and that you have received the permissions necessary to include the work of others in the Article; and
- That the Article does not libel or violate the privacy rights of any third party.