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3. Human iPSC–liver organoid transplantation reduces fibrosis through immunomodulation.

Author

Tadokoro, Tomomi, Murata, Soichiro, Kato, Mimoko, Ueno, Yasuharu, Tsuchida, Tomonori, Okumura, Ayumu, Kuse, Yoshiki, Konno, Takahiro, Uchida, Yutaro, Yamakawa, Yuriko, Zushi, Marina, Yajima, Megumi, Kobayashi, Tatsuya, Hasegawa, Shunsuke, Kawakatsu-Hatada, Yumi, Hayashi, Yoshihito, Osakabe, Shun, Maeda, Takuji, Kimura, Kodai, and Mori, Akihiro

Subjects
INDUCED pluripotent stem cells, HEPATIC fibrosis, BILE ducts, CELL communication, FETAL tissues
Abstract

Donor organ shortages for transplantation remain a serious global concern, and alternative treatment is in high demand. Fetal cells and tissues have considerable therapeutic potential as, for example, organoid technology that uses human induced pluripotent stem cells (hiPSCs) to generate unlimited human fetal-like cells and tissues. We previously reported the in vivo vascularization of early fetal liver–like hiPSC-derived liver buds (LBs) and subsquent improved survival of recipient mice with subacute liver failure. Here, we show hiPSC–liver organoids (LOs) that recapitulate midgestational fetal liver promote de novo liver generation when grafted onto the surface of host livers in chemical fibrosis models, thereby recovering liver function. We found that fetal liver, a hematopoietic tissue, highly expressed macrophage-recruiting factors and antifibrotic M2 macrophage polarization factors compared with the adult liver, resulting in fibrosis reduction because of CD163+ M2-macrophage polarization. Next, we created midgestational fetal liver–like hiPSC-LOs by fusion of hiPSC-LBs to induce static cell-cell interactions and found that these contained complex structures such as hepatocytes, vasculature, and bile ducts after transplantation. This fusion allowed the generation of a large human tissue suitable for transplantation into immunodeficient rodent models of liver fibrosis. hiPSC-LOs showed superior liver function compared with hiPSC-LBs and improved survival and liver function upon transplantation. In addition, hiPSC-LO transplantation ameliorated chemically induced liver fibrosis, a symptom of liver cirrhosis that leads to organ dysfunction, through immunomodulatory effects, particularly on CD163+ phagocytic M2-macrophage polarization. Together, our results suggest hiPSC-LO transplantation as a promising therapeutic option for liver fibrosis. Editor's summary: Human induced pluripotent stem cells (hiPSCs) show clear potential for regenerative medicine, but their clinical development can be challenging. Tadokoro et al. show that fusion of hundreds of hiPSC-derived fetal liver–like buds produces larger organoids that are suitable for transplantation. Engraftment of these fused organoids onto the livers of immunocompromised mice resulted in the formation of bile duct and other liver structures, as well as connections between the human organoid and mouse liver vasculatures. These grafts partially reverted chemically induced liver fibrosis in the mice through phagocytic macrophage polarization, indicating a promising therapeutic approach that should be further tested in preclinical models of metabolic liver disease. —Catherine Charneski [ABSTRACT FROM AUTHOR]

Published
2024
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21. Pulmonary solid adenocarcinoma in a dog

Author

Michishita, Masaki, primary, Hanari, Naoki, additional, Oda, Hitomi, additional, Nagashima, Tomokazu, additional, Machida, Yukino, additional, Hamamoto, Yuji, additional, Tamura, Kyoichi, additional, Azakami, Daigo, additional, Ochiai, Kazuhiko, additional, and Mori, Akihiro, additional

Published
2023
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28. Logical DP Matching for Detecting Similar Subsequence

Author

Uchida, Seiichi, Mori, Akihiro, Kurazume, Ryo, Taniguchi, Rin-ichiro, Hasegawa, Tsutomu, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Yagi, Yasushi, editor, Kang, Sing Bing, editor, Kweon, In So, editor, and Zha, Hongbin, editor

Published
2007
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31. A Feasibility Study on the Simultaneous Sensing of Turbidity and Chlorophyll a Concentration Using a Simple Optical Measurement Method

Author

Isoyama, Ryota, Taie, Manami, Kageyama, Tomoaki, Miura, Masashi, Maeda, Akihiro, Mori, Akihiro, Lee, Sang-Seok, Isoyama, Ryota, Taie, Manami, Kageyama, Tomoaki, Miura, Masashi, Maeda, Akihiro, Mori, Akihiro, and Lee, Sang-Seok

Abstract

We have been developing a wireless sensor network system to monitor the quality of lake water in real time. It consists of a sensor module and a system module, which includes communication and power modules. We have focused on pH, turbidity and chlorophyll a concentration as the criteria for qualifying lake water quality. These parameters will be detected by a microfluidic device based sensor module embedded in the wireless sensor network system. In order to detect the turbidity and the chlorophyll a concentration simultaneously, we propose a simple optical measurement method using LED and photodiode in this paper. Before integrating a turbidity and chlorophyll a concentration sensor into the microfluidic device based pH sensor, we performed feasibility studies such as confirmation of the working principle and experiments using environmental water samples. As a result, we successfully verified our simultaneous sensing method by using a simple optical setup of the turbidity and the chlorophyll a concentration.

Published
2022

34. Efficacy and safety of 3 day versus 7 day cefditoren pivoxil regimens for acute uncomplicated cystitis: multicentre, randomized, open-label trial

Author

Sadahira, Takuya, Wada, Koichiro, Araki, Motoo, Ishii, Ayano, Takamoto, Atsushi, Kobayashi, Yasuyuki, Watanabe, Masami, Watanabe, Toyohiko, Nasu, Yasutomo, Kumon, Hiromi, Nasu, Yasutomo, Akaeda, Teruaki, Akazawa, Nobuyuki, Akebi, Naoki, Araki, Daiji, Araki, Tohru, Araki, Motoo, Arata, Ryoji, Ariyoshi, Yuichi, Ando, Eiichi, Ando, Nobuyoshi, Ishii, Ayano, Ishii, Kazushi, Ishikawa, Tsutomu, Ishito, Noritaka, Ichikawa, Takaharu, Inoue, Takaaki, Inoue, Miyabi, Inoue, Yosuke, Irie, Shin, Iwata, Takehiro, Uesugi, Tatsuya, Uehara, Shinya, Uematsu, Katsutoshi, Uno, Satoshi, Edamura, Kohei, Ebara, Shin, Oiwa, Yuko, Oeda, Tadashi, Ohashi, Teruhisa, Ohashi, Yozo, Ozawa, Hideo, Ochi, Junzo, Ono, Noriaki, Kai, Seiji, Kaku, Haruki, Katayama, Satoshi, Katayama, Yasuhiro, Kaneshige, Tetuzo, Kawauchi, Keiichiro, Kawaguchi, Masashi, Kawada, Tatsushi, Kanbara, Taiki, Kishi, Mikio, Kishimoto, Ryo, Kusaka, Nobuyuki, Kusumi, Norihiro, Kunitomi, Kimito, Kubota, Risa, Kumon, Hiromi, Kurahashi, Hiroaki, Kojima, Hironori, Kobayashi, Tomoko, Kobayashi, Yasuyuki, Kobuke, Makoto, Kondo, Katsuyoshi, Saika, Takashi, Sakaeda, Kazuma, Sakuramoto, Koji, Sako, Shinichi, Sako, Tomoko, Sasaoka, Taketo, Sasaki, Katsumi, Sadahira, Takuya, Jo, Yoshimasa, Sugimoto, Morito, Seno, Yuko, Takao, Akira, Takamura, Kosuke, Takamura, Kousuke, Takamoto, Atsushi, Takamoto, Hitoshi, Takeda, Katsuji, Takenaka, Tadasu, Tanaka, Daisuke, Tanimoto, Ryuta, Tsugawa, Masaya, Tsushima, Tomoyasu, Tsuboi, Hiromu, Tojo, Syunji, Tokinaga, Kenji, Tominaga, Yusuke, Doi, Keisuke, Nagai, Atsushi, Nakajima, Hirochika, Nakada, Tetsuya, Nakatsuka, Hirokazu, Nakamura, Aya, Nakayama, Yasuki, Nasu, Yoshitsugu, Nishikawa, Daisuke, Nishiguchi, Jun, Nishitani, Yoshio, Nishimura, Shingo, Nishimura, Motoichi, Nishiyama, Yasuhiro, Nibuno, Hajime, Nozaki, Kunihiro, Nose, Hiroyuki, Noda, Gaku, Hashimoto, Hideaki, Hata, Kazuhiro, Hayashi, Toshihide, Hayashi, Nobuki, Hayata, Syunji, Hara, Ryoei, Hirata, Takeshi, Fujii, Tomohiro, Fujio, Kei, Fujita, Ryuji, Bekku, Kensuke, Maehara, Takanori, Maki, Yoshio, Matsumoto, Yuko, Manabe, Daisuke, Mayumi, Yusuke, Maruyama, Yuki, Mitsui, Yosuke, Miyaji, Sadayuki, Munemasa, Syuhei, Murao, Wataru, Murakami, Takanori, Murata, Tadashi, Mori, Akihiro, Morita, Akira, Monden, Koichi, Yamasaki, Tomoya, Yamashita, Masahiro, Yamada, Daiduke, Yamato, Toyoko, Yamane, Toru, Yamanoi, Tomoaki, Yamamoto, Yasuo, Yukari, Kazuaki, Yokoyama, Teruhiko, Yoshioka, Takashi, Watanabe, Toyohiko, Watanabe, Masami, Watanabe, Yuichi, and Wada, Koichiro

Published
2017
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