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Published Online: 13 October 2022

Autologous Bilayered Adipose-Derived Mesenchymal Cell-Gelatin Sheets Reconstruct Ureters in Rabbits

Publication: Tissue Engineering Part A
Volume 28, Issue Number 19-20


Repair of ureteral defects or strictures due to disease or trauma is usually dependent upon surgery that often requires either reoperation or an alternative treatment. By taking advantage of tissue engineering and regenerative techniques, it may be possible to define new approaches to ureteral repair. In this study, we fabricated autologous bilayered adipose-derived mesenchymal cell (AMC)-gelatin sheets and transplanted them into rabbits to replace surgically excised ureteral segments. AMCs harvested from abdominal adipose tissues of female New Zealand white rabbits were cultured on collagen-coated dishes and labeled with PKH26, a red fluorescent dye, for later identification. Monolayers of the cultured PKH26-labeled AMCs were detached and applied to gelatin hydrogel sheets. Two gelatin sheets were then united with the AMC monolayers apposed together, forming a bilayered AMC-gelatin sheet. Following each partial ureterectomy, a bilayered autologous AMC-gelatin sheet was transplanted, joining the proximal and distal ends of the remaining ureter (n = 9). Control animals underwent the same procedure except that the transplant was achieved with a bilayered acellular-gelatin sheet (n = 9). At 4 and 8 weeks after transplantation, the proximal regions of ureters treated with the control bilayered acellular-gelatin sheets exhibited flexures and dilations, which are not characteristic of unoperated ureters. In contrast, the bilayered AMC-gelatin sheet-transplanted rabbits did not have ureteral flexures or dilations. About midway between the proximal and distal ends, both the control and experimental reconstructed ureteral walls had smooth muscle layers; however, those in the experimental reconstructed ureteral walls were significantly thicker and better organized than those in the control reconstructed ureteral walls. Some AMCs differentiated into smooth muscle marker-positive cells. The experimental ureteral walls contained smooth muscle cells derived from the PKH26-labeled AMCs and others that were derived through migration and differentiation of cells from the remaining proximal and distal ends of the original ureter. In addition, the lumina of the 8-week reconstructed ureteral tissues in experimental rabbits did not show histological strictures as seen in the control ureters. These results suggest that the bilayered AMC-gelatin sheets have the potential to replace defective tissues and/or reconstruct damaged ureters.

Impact Statement

To reconstruct ureter tissues following partial ureterectomy, we fabricated bilayered adipose-derived mesenchymal cell (AMC)-gelatin sheets based on cell sheet engineering principles. The bilayered AMC-gelatin sheets were transplanted into rabbits to replace a surgically excised ureteral segment. At 4 and 8 weeks after, the ureters that received bilayered AMC-gelatin sheets did not exhibit severe flexures, dilations, or strictures. The experimental ureteral walls had smooth muscle marker-positive cells that were differentiated from the AMCs, and similar cells were present in the adjacent intact ureteral tissues. Therefore, the bilayered AMC-gelatin sheets have the potential to reconstruct ureters damaged through disease or trauma.

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Information & Authors


Published In

cover image Tissue Engineering Part A
Tissue Engineering Part A
Volume 28Issue Number 19-20October 2022
Pages: 855 - 866
PubMed: 35850515


Published online: 13 October 2022
Published in print: October 2022
Published ahead of print: 16 September 2022
Published ahead of production: 19 July 2022
Accepted: 13 June 2022
Received: 26 April 2022


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    Noriyuki Ogawa, MD
    Department of Urology, Shinshu University School of Medicine, Nagano, Japan.
    Department of Urology, Shinshu University School of Medicine, Nagano, Japan.
    Tomonori Minagawa, MD, PhD
    Department of Urology, Shinshu University School of Medicine, Nagano, Japan.
    Teruyuki Ogawa, MD, PhD
    Department of Urology, Shinshu University School of Medicine, Nagano, Japan.
    Osamu Ishizuka, MD, PhD
    Department of Urology, Shinshu University School of Medicine, Nagano, Japan.


    Address correspondence to: Tetsuya Imamura, PhD, Department of Urology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan [email protected]

    Disclosure Statement

    No competing financial interests exist.

    Funding Information

    No funding was received for this article.

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