Authors:
Eiji Kobayashi Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

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Shin Enosawa Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

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Abstract:

Introduction: Research has made progress in organ fabrication using an extracellular matrix, cell sheets, or organoids. Human liver tissue has been constructed using a 3-dimensional (3D) bioprinter and showed evidence that an in vitro generated liver bud was reformed in a rodent liver model. This study describes the stages of development of rat fetal organs and liver structure and reviews recent progress in liver organoid transplantation. Methods: The authors developed the procedures for creating a transected plane for use in experimental microsurgery in rats. A liver lobe was fixed vertically with gauze and it was ligated with 6-0 silk suture in the cut line; the parenchyma was cut, and major vessels were ligated to create the transected plane. The ligated tissue was carefully resected. Hemostasis was not required and hepatic components remained on the transected plane. The plane was covered by omentum. Results: Using this model, we transplanted fetal liver or a 3D bioprinted liver organoid. This microsurgical method enabled creation of an intact liver parenchyma plane. No bleeding was observed. The transplanted liver components successfully engrafted on the liver. Conclusion: This method may provide an essential environment for growing liver using portal and arterial blood flow.

  • 1

    Tohyama S, Fujita J, Fujita C, Fujita C, Yamaguchi M, Kanaami S, Ohno R, Sakamoto K, Kodama M, Kurokawa J, Kanazawa H, Seki T, Kishino Y, Okada M, Nakajima K, Tanosaki S, Someya S, Hirano A, Kawaguchi S, Kobayashi E, Fukuda K: Efficient large-scale 2D culture system for human induced pluripotent stem cells and differentiated cardiomyocytes. Stem Cell Reports 2017; 9: 1406–1414.

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  • 2

    Camp JG, Sekine K, Gerber T, Loeffler-Wirth H, Binder H, Gac M, Kanton S, Kageyama J, Damm G, Seehofer D, Belicova L, Bickle M, Barsacchi R, Okuda R, Yoshizawa E, Kimura M, Ayabe H, Taniguchi H, Takebe T, Treutlein B: Multilineage communication regulates human liver bud development from pluripotency. Nature 2017; 546: 533–538.

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  • 3

    Kobayashi E: Challenges for production of human transplantable organ grafts. Cell Med. 2016; 9: 9–14.

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  • 4

    Hata T, Uemoto S, Fujimoto Y, Murakami T, Tateno C, Yoshizato K, Kobayashi E.: Transplantation of engineered chimeric liver with autologous hepatocytes and xenobiotic scaffold. Ann Surg. 2013; 257: 542–547.

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  • 5

    Yamaguchi T, Sato H, Kato-Itoh M, Goto T, Hara H, Sanbo M, Mizuno N, Kobayashi T, Yanagida A, Umino A, Ota Y, Hamanaka S, Masaki H, Rashid ST, Hirabayashi M, Nakauchi H: Interspecies organogenesis generates autologous functional islets. Nature. 2017; 542: 191–196.

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  • 6

    Wu J, Platero-Luengo A, Sakurai M, Sugawara A, Gil MA, Yamauchi T, Suzuki K, Bogliotti YS, Cuello C, Morales Valencia M, Okumura D, Luo J, Vilariño M, Parrilla I, Soto DA, Martinez CA, Hishida T, Sánchez-Bautista S, Martinez-Martinez ML, Wang H, Nohalez A, Aizawa E, Martinez-Redondo P, Ocampo A, Reddy P, Roca J, Maga EA, Esteban CR, Berggren WT, Nuñez Delicado E, Lajara J, Guillen I, Guillen P, Campistol JM, Martinez EA, Ross PJ: Interspecies chimerism with mammalian pluripotent stem cells. Cell. 2017; 168: 473–486.e15.

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  • 7

    Sekine H, Shimizu T, Sakaguchi K, Dobashi I, Wada M, Yamato M, Kobayashi E, Umezu M, Okano T:In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels. Nat Commun. 2013; 4: 1399.

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  • 8

    Yokote S, Matsunari H, Iwai S, Yamanaka S, Uchikura A, Fujimoto E, Matsumoto K, Nagashima H, Kobayashi E, Yokoo T: Urine excretion strategy for stem cell-generated embryonic kidneys. Proc Natl Acad Sci U S A 2015; 112: 12980–12985.

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  • 9

    Yanagi Y, Nakayama K, Taguchi T, Enosawa S, Tamura T, Yoshimaru K, Matsuura T, Hayashida M, Kohashi K, Oda Y, Yamaza T, Kobayashi E:In vivo and ex vivo methods of growing a liver bud through tissue connection. Sci Rep. 2017; 7: 14085.

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  • 10

    Fujimoto E, Yamanaka S, Kurihara S, Tajiri S, Izuhara L, Katsuoka Y, Yokote S, Matsumoto K, Kobayashi E, Okano HJ, Chikaraishi T, Yokoo T: Embryonic kidney function in a chronic renal failure model in rodents. Clin Exp Nephrol. 2017; 21: 579–588.

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  • 11

    Taguchi A, Nishinakamura R: Higher-order kidney organogenesis from pluripotent stem cells. Cell Stem Cell 20175909: 30428–30429.

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  • 12

    Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, Zhang RR, Ueno Y, Zheng YW, Koike N, Aoyama S, Adachi Y, Taniguchi H: Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 2013; 499: 481–484.

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  • 13

    Ota Y, Kumamoto T, Ishibe A, Watanabe K, Mori R, Taniguchi K, Matsuyama R, Makino H, Ueda M, Kubota T, Akiyama H, Tanaka K, Ichikawa Y, Endo I: Thrombomodulin improves rat survival after extensive hepatectomy. J Surg Res. 2015; 194: 375–82.

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