Future Prospects for Human Tissue Engineered Urethra Transplantation: Decellularization and Recellularization-Based Urethra Regeneration

Abstract

To evaluate the histological characteristics of decellularized human urethra after transplantation into the rat omentum and compare in vivo cell seeding with perfusion-based and cell sheet urethral regeneration. Eight adult human male urethras accompanied with the surrounding corpus spongiosum were obtained. The tissues were decellularized with detergent-based method. The efficacy of decellularization and extracellular matrix preservation was evaluated by several techniques. Decellularized scaffolds were transplanted into the omentum of 12 male rats and located into the scrotum. Biopsies were taken 1, 3, and 6 months postoperatively to assess the natural recellularization. Mesenchymal stem cells obtained from preputial tissue were seeded with perfusion-based and cell sheet techniques as well. Immunohistochemical staining with α-actin, cytokeratin AE1/AE3, synaptophysin, and CD31 antibodies were performed. Removal of nuclear components and preservation of biomechanical properties was confirmed. In-vivo recellularization revealed promising results in progressive angiogenesis and cell seeding of epithelium-like cells in the lining of the urethra as well as smooth muscle cells in the wall structure. In-vitro urethral regeneration revealed that cell sheet engineering was the technique of choice compared to perfusion-based technique. This study may paw the road for clinical application of acellular urethral matrix with the surrounding corpus spongiosum in urological reconstructive surgery.

Complete Human Penile Scaffold for Composite Tissue Engineering: Organ Decellularization and Characterization

“…In two separate projects, Kajbafzadeh et al . in 2017 isolated human cavernosa 28 and urethra 29 respectively for decellularization and successfully demonstrated small animal biocompatibility. The scaffold reported in our study is substantially more complex than any reported to date due to both (1) the anatomical complexity and increased scaffold diameter from using the whole organ with corpora and urethra rather than only one sub-unit and (2) the use of human penile specimens, with far greater scaffold size representing an additional obstacle but also an essential step to clinical translation.…”

Tissue-Engineered Grafts from Human Decellularized Extracellular Matrices: A Systematic Review and Future Perspectives

“…In vivo recellularization was performed through transplantation of a section of decellularized scaffold into the omentum of adult rats and location into the scrotum; good endothelial and smooth muscle cell recellularization was achieved after six months. An analogous approach was also followed by the same research group for decellularization and in vivo recellularization of human urethra surrounded by its corpus spongiosum [277]. In this second work, however, in vitro recellularization was also performed with mesenchymal stem cells for preputial tissue, through static-based or perfusion-based procedures.…”

Tissue engineering of the urethra: where are we in 2019?

“…The most important factors in assessing the outcome of a new tissue engineering procedure is careful background basic research, the appropriate use of animal models [30,31] and the comprehensive long-term follow-up of patients. A further important issue is the increased recognition in recent years that when cells, particularly stem cells, are harvested and placed in a new tissue environment then they can change their phenotype.…”