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Theranostics 2017; 7(9):2509-2523. doi:10.7150/thno.18833 This issue Cite

Research Paper

Fabrication of Tissue-Engineered Bionic Urethra Using Cell Sheet Technology and Labeling By Ultrasmall Superparamagnetic Iron Oxide for Full-Thickness Urethral Reconstruction

Shukui Zhou¹, Ranxin Yang¹, Qingsong Zou¹, Kaile Zhang¹, Ting Yin², Weixin Zhao³, Joseph G. Shapter⁴, Guo Gao^2✉, Qiang Fu^1✉

1. Department of Urology, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China;
2. Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Technology, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China;
3. Wake Forest Institute for Regenerative Medicine, Winston Salem, NC, USA;
4. School of Chemical and Physical Sciences, Flinders University, Bedford Park, Adelaide 5042, Australia.

✉ Corresponding authors: Qiang Fu, Department of Urology, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China. ZIP: 200233. Fax: 021-63868708, E-mail address: jamesqfucom (Q. Fu). Guo Gao, E-mail address: guogaoedu.cn (G. Gao). More

Abstract

Urethral strictures remain a reconstructive challenge, due to less than satisfactory outcomes and high incidence of stricture recurrence. An “ideal” urethral reconstruction should establish similar architecture and function as the original urethral wall. We fabricated a novel tissue-engineered bionic urethras using cell sheet technology and report their viability in a canine model. Small amounts of oral and adipose tissues were harvested, and adipose-derived stem cells, oral mucosal epithelial cells, and oral mucosal fibroblasts were isolated and used to prepare cell sheets. The cell sheets were hierarchically tubularized to form 3-layer tissue-engineered urethras and labeled by ultrasmall super-paramagnetic iron oxide (USPIO). The constructed tissue-engineered urethras were transplanted subcutaneously for 3 weeks to promote the revascularization and biomechanical strength of the implant. Then, 2 cm length of the tubularized penile urethra was replaced by tissue-engineered bionic urethra. At 3 months of urethral replacement, USPIO-labeled tissue-engineered bionic urethra can be effectively detected by MRI at the transplant site. Histologically, the retrieved bionic urethras still displayed 3 layers, including an epithelial layer, a fibrous layer, and a myoblast layer. Three weeks after subcutaneous transplantation, immunofluorescence analysis showed the density of blood vessels in bionic urethra was significantly increased following the initial establishment of the constructs and was further up-regulated at 3 months after urethral replacement and was close to normal level in urethral tissue. Our study is the first to experimentally demonstrate 3-layer tissue-engineered urethras can be established using cell sheet technology and can promote the regeneration of structural and functional urethras similar to normal urethra.

Keywords: tissue engineering, cell sheet technology, bionic urethra, urethral reconstruction, transplant imaging, ultrasmall super-paramagnetic iron oxide (USPIO).

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