Abstract
Engineering three-dimensional tissues in vitro for regenerative therapy is highly desired. Vascular beds with connectable arteries and veins play crucial roles in fabricating three-dimensional tissues in vitro and improving the survival rate of transplanted three-dimensional tissues in vivo. Here, we developed a method to reconstruct a new vascular bed that could be implanted into humans for clinical applications. Porcine small intestine with an arteriovenous loop was selected as a vascular bed skeleton and decellularized using transvascular perfusion with both detergent and enzyme. Subsequently, the decellularized intestinal graft was re-endothelialized with human cells to allow blood perfusion into the vascular bed. The small intestinal graft was successfully decellularized without severe damage to the burst pressure of the graft, and the decellularized intestinal graft could be transplanted without a severe inflammatory response in rats for two weeks. In addition, the decellularized intestinal graft was partially vascularized with human endothelial cells in seven days. Therefore, the reconstructed intestinal vascular bed may serve as a human transplantable vascular bed with potential in clinical investigations.
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Acknowledgments
This research was supported by the “Development of innovative manufacturing technology for three-dimensional tissues and organs based on cell sheet engineering” from the Japan Agency for Medical Research and Development (AMED, https://www.amed.go.jp/en/index.html; grant no. JP17he0702249) and JSPS KAKENHI Grant Number JP 18J22398. We would like to thank Editage (www.editage.com) for English language editing.
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Kazunori Sano is an employee of Tokai Hit Co., Ltd (Japan). Tatsuya Shimizu is a member of the scientific advisory board and a shareholder of CellSeed Inc. (Japan). Tokyo Women’s Medical University received research funds from CellSeedInc. Tokyo Women’s Medical University received a research grant from Tokaihit Co., Ltd, Japan.
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Tobe, Y. et al. (2021). Reconstruction of a Vascular Bed with Perfusable Blood Vessels Using a Decellularized Porcine Small Intestine for Clinical Application. In: Shiraishi, Y., Sakuma, I., Naruse, K., Ueno, A. (eds) 11th Asian-Pacific Conference on Medical and Biological Engineering. APCMBE 2020. IFMBE Proceedings, vol 82. Springer, Cham. https://doi.org/10.1007/978-3-030-66169-4_35
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DOI: https://doi.org/10.1007/978-3-030-66169-4_35
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