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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

Abstract

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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References

1. Gild P, Kluth LA, Vetterlein MW, et al. Adult iatrogenic ureteral injury and stricture-incidence and treatment strategies. Asian J Urol 2018;5(2):101–106;.
2. Buffi N, Cestari A, Lughezzani G, et al. Robot-assisted uretero-ureterostomy for iatrogenic lumbar and iliac ureteral stricture: Technical details and preliminary clinical results. Eur Urol 2011;60(6):1221–1225;.
3. Mauck RJ, Hudak SJ, Terlecki RP, et al. Central role of Boari bladder flap and downward nephropexy in upper ureteral reconstruction. J Urol 2011;186(4):1345–1349;.
4. Xiong S, Wang J, Zhu W, et al. Onlay repair technique for the management of ureteral strictures: A comprehensive review. Biomed Res Int 2020;2022:6178286;.
5. Langer R, Vacanti J. Advances in tissue engineering. J Pediatr Surg 2016;51(1):8–12;.
6. Bertanha M, Moroz A, Almeida R, et al. Tissue-engineered blood vessel substitute by reconstruction of endothelium using mesenchymal stem cells induced by platelet growth factors. J Vasc Surg 2014;59(6):1677–1685;.
7. Silva JM, Rodrigues LC, Silva SS, et al. Engineered tubular structures based on chitosan for tissue engineering applications. J Biomater Appl 2018;32(7):841–852;.
8. Sang J, Li X, ShaoY, et al. Controlled tubular unit formation from collagen film for modular tissue engineering. ACS Biomater Sci Eng 2017;3(11):2860–2868;.
9. Stefani I, Cooper-White JJ. Development of an in-process UV-crosslinked, electrospun PCL/aPLA-co-TMC composite polymer for tubular tissue engineering applications. Acta Biomater 2016;36:231–240;.
10. Xu S, Li Q, Pan H, et al. Tubular Silk fibroin/gelatin-tyramine hydrogel with controllable layer structure and its potential application for tissue engineering. ACS Biomater Sci Eng 2020;6(12):6896–6905;.
11. Kim IG, Park SA, Lee SH, et al. Transplantation of a 3D-printed tracheal graft combined with iPS cell-derived MSCs and chondrocytes. Sci Rep 2020;10(1):4326;.
12. Versteegden LR, van Kampen KA, Janke HP. Tubular collagen scaffolds with radial elasticity for hollow organ regeneration. Acta Biomater 2017;52:1–8;.
13. Imashiro C, Shimizu T. Fundamental technologies and recent advances of cell-sheet-based tissue engineering. Int J Mol Sci 2021;22(1):425;.
14. Kobayashi J, Kikuchi A, Aoyagi T, et al. Cell sheet tissue engineering: Cell sheet preparation, harvesting/manipulation, and transplantation. J Biomed Mater Res A 2019;107(5):955–967;.
15. Nakamura K, Saotome T, Shimada N, et al. A gelatin hydrogel nonwoven fabric facilitates metabolic activity of multilayered cell sheets. Tissue Eng Part C Methods 2019;25(6):344–352;.
16. Imamura T, Yamamoto T, Ishizuka O, et al. The microenvironment of freeze-injured mouse urinary bladders enables successful tissue engineering. Tissue Eng Part A 2009;15(11):3367–3375;.
17. Bou-Ghannam S, Kim K, Grainger DW, et al. 3D cell sheet structure augments mesenchymal stem cell cytokine production. Sci Rep 2021;11(1):8170;.
18. Arora S, Campbell L, Tourojman M, et al. Robotic buccal mucosal graft ureteroplasty for complex ureteral stricture. Urology 2017;110:257–258;.
19. Li B, Xu Y, Hai B, et al. Laparoscopic onlay lingual mucosal graft ureteroplasty for proximal ureteral stricture: Initial experience and 9-month follow-up. Int Urol Nephrol 2016;48(8):1275–1279;.
20. Gomez-Avraham I, Nguyen T, Drach GW. Ileal patch ureteroplasty for repair of ureteral strictures: Clinical application and results in 4 patients. J Urol 1994;152(6 Pt 1):2000–2004;.
21. Wang J, Xiong S, Fan S, et al. Appendiceal onlay flap ureteroplasty for the treatment of complex ureteral strictures: Initial experience of nine patients. J Endourol 2020;34(8):874–881;.
22. Macauley RJ, Frohbose WJ. The surgical correction of ureteropelvic junction obstruction using a free graft of renal pelvis wall. J Urol 1970;104(1):67–70;.
23. Zou L, Mao S, Liu S, et al. Ureteral reconstruction using a tapered non-vascularized bladder graft: An experimental study in a canine animal model. BMC Urol 2017;17(1):97;.
24. Hussein MM, Almogazy H, Mamdouh A, et al. Urethroplasty for treatment of long anterior urethral stricture: Buccal mucosa graft versus penile skin graft-does the stricture length matter? Int Urol Nephrol 2016;48(11):1831–1835;.
25. Onal B, Gultekin MH, Simsekoglu MF. Preputial graft ureteroplasty for the treatment of complex ureteral stricture: A new surgical technique and review of literature. J Endourol Case Rep 2018;4(1):136–139;.
26. Robbins AK, Mateson AB, Khandha A, et al. Fetal rat gubernaculum mesenchymal cells adopt myogenic and myofibroblast-like phenotypes. J Urol 2016;196(1):270–278;.
27. Ryu B, Sekine H, Homma J, et al. Allogeneic adipose-derived mesenchymal stem cell sheet that produces neurological improvement with angiogenesis and neurogenesis in a rat stroke model. J Neurosurg 2019;132(2):442–455;.
28. Nakamura Y, Ishikawa H, Kawai K, et al. Enhanced wound healing by topical administration of mesenchymal stem cells transfected with stromal cell-derived factor-1. Biomaterials 2013;34(37):9393–9400;.
29. Linero I, Chaparro O. Paracrine effect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS One 2014;9(9):e107001;.
30. Liu Y, Liu X, Ye P, et al. MicroRNA-191 regulates differentiation and migration of mesenchymal stem cells and their paracrine effect on angiogenesis. Biotechnol Lett 2020;42(9):1777–1788;.
31. Xiang E, Han B, Zhang Q, et al. Human umbilical cord-derived mesenchymal stem cells prevent the progression of early diabetic nephropathy through inhibiting inflammation and fibrosis. Stem Cell Res Ther 2020;11(1):336;.
32. Ishiuchi N, Nakashima A, Doi S, et al. Hypoxia-preconditioned mesenchymal stem cells prevent renal fibrosis and inflammation in ischemia-reperfusion rats. Stem Cell Res Ther 2020;11(1):130;.

Information & Authors

Information

Published In

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

History

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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    Authors

    Affiliations

    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.

    Notes

    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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