Cell-Seeded Acellular Artery for Reconstruction of Long Urethral Defects in a Canine Model

Abstract

The management of urethral stricture remains a major therapeutic challenge in clinics. Herein, we explored the feasibility of reconstructing a relatively long segment of the urethra by the cell-seeded acellular artery in a canine model. The acellular arterial matrix was obtained from the excised carotid artery of donor dogs. Autologous adipose-derived stem cells (ADSCs) from 6 male dogs were grown and seeded onto the premade acellular arterial matrix. A 3 cm long segment of the urethra was resected in 12 male dogs. Urethroplasty was performed with the acellular arterial matrix seeded with ADSCs in 6 animals and without cells in 6. Serial urethrography was performed at 1 and 3 months postoperatively. Wide urethral calibers without any signs of strictures were confirmed in all 6 animals in the experimental group. In contrast, urethral stricture was demonstrated in 3 animals in the control group. The graft was highly epithelialized and smooth in the experimental group, while graft contracture and scar formation were showed in the control group. Histologic analysis of the cell-seeded arterial matrix at 1 month confirmed the presence of multilayered urothelium and muscle. The levels of tissue formation developed over time with a progressive increase in muscle content. In contrast, extensive fibrosis and sparse smooth muscle were seen in animals treated with matrix without ADSCs. This study provides preclinical evidence that the ADSC-seeded arterial matrix can be used as a tubularized scaffold in the reconstruction of 3 cm long urethral defect in a male canine model. The ADSC-seeded arterial matrix remodels and regenerates normal-appearing urethral tissue layers over time.

Ascorbic Acid 2-Phosphate-Releasing Supercritical Carbon Dioxide-Foamed Poly(L-Lactide-Co-epsilon-Caprolactone) Scaffolds Support Urothelial Cell Growth and Enhance Human Adipose-Derived Stromal Cell Proliferation and Collagen Production

“…Along with the mature urothelium, the regeneration of stromal tissue and smooth muscle layers is critical for functional urethra [26][27][28][29], and therefore, we utilized hASC for the stromal compartment in our study. A2P in scPLCL A2P had a noticeable efect on hASC viability and proliferation.…”

“…Previous preclinical studies have demonstrated that cell seeding is benefcial in urethral tissue engineering [19,[26][27][28][29][30]. Most importantly, the use of adipose-derived stromal/stem cells (ASCs) or smooth muscle cells has been shown to enhance angiogenesis and the formation of the urethral stromal tissue during the tissue regeneration, inhibiting the formation of urethral fbrosis [26][27][28][29].…”

“…Previous preclinical studies have demonstrated that cell seeding is benefcial in urethral tissue engineering [19,[26][27][28][29][30]. Most importantly, the use of adipose-derived stromal/stem cells (ASCs) or smooth muscle cells has been shown to enhance angiogenesis and the formation of the urethral stromal tissue during the tissue regeneration, inhibiting the formation of urethral fbrosis [26][27][28][29]. Besides ASCs, several cell types have been utilized in urethral tissue engineering research, including fbroblasts [31,32], smooth muscle cells [27,33,34], stromal/stem cells [35][36][37][38] along with urothelial cells (UCs) [10,[39][40][41][42].…”

“…As such, they are appealing cell alternatives to smooth muscle cells for forming urethral stromal tissue. Moreover, ASCs and other mesenchymal stem and progenitor cells are capable of reducing infammation and promoting angiogenesis and intrinsic tissue regeneration in situ [29,48,49].…”

Cell-Based Therapy for Urethral Regeneration: A Narrative Review and Future Perspectives

“…ADSC composite scaffolds have also undergone significant improvements. In one study, autologous ADSCs from dogs were grown and seeded onto a premade acellular arterial matrix [ 67 ]. Seeded scaffolds were used to repair surgically produced urethral defects in six male dogs, and the results were compared with those of six control animals treated with the acellular arterial matrix.…”