Transplantation · 2026
Oxygenated Perfusion Enhances Hepatocyte Function in Human iPSC-liver Tissue.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Yamabe Soichiro, Kuse Yoshiki, Okumura Takashi, Kasai Toshiharu, Nishi Kotaro, Tsuchida Tomonori, Ohtomo Mana, Yagi Hiroshi, Sakai Hiromi, Yamaguchi Kiyoshi, Furukawa Yoichi, Tanimizu Naoki, Taniguchi Hideki
Аннотация
BACKGROUND: Organ transplantation remains the only curative treatment for end-stage organ failure. However, a critical shortage of donor organs presents a major challenge. Human induced pluripotent stem cell (hiPSC)-derived organoids represent a promising technology for generating transplantable human tissues. This study aimed to create functional and scalable tissue from hiPSC-derived liver organoids (hiPSC-LOs) by establishing an oxygenation system using a decellularized liver (DL), which retains the parenchymal and vascular extracellular matrix to support cell adhesion and medium perfusion.
METHODS: First, the culture condition of hiPSC-LOs was refined to enhance their engraftment in rat DLs. Next, an oxygenation system for hiPSC-LO-engrafted DLs (hiPSC-liver tissue [hiPSC-LT]) was established using perfusion of oxygen-enriched medium containing artificial red blood cells. Finally, the oxygenated hiPSC-LTs were transplanted onto the liver surface of immunodeficient mice.
RESULTS: Functional hiPSC-LTs were successfully generated by infusing day 8 precultured hiPSC-LOs into DLs. Perfusion with oxygenated medium containing artificial red blood cells suppressed cell death and promoted hepatic function of hiPSC-LTs by mimicking the physiological oxygen concentration found in the fetal liver. Notably, oxygenated hiPSC-LTs demonstrated improved engraftment in vivo, as evidenced by increased human albumin levels in recipient mouse serum compared with nonoxygenated controls.
CONCLUSIONS: The oxygenation system using DLs and artificial red blood cells effectively supported the generation of transplantable, functional hiPSC-LT. This culture strategy enhances both the enlargement and functionality of hiPSC-organoids and represents a promising step toward developing alternatives to conventional organ transplantation.
METHODS: First, the culture condition of hiPSC-LOs was refined to enhance their engraftment in rat DLs. Next, an oxygenation system for hiPSC-LO-engrafted DLs (hiPSC-liver tissue [hiPSC-LT]) was established using perfusion of oxygen-enriched medium containing artificial red blood cells. Finally, the oxygenated hiPSC-LTs were transplanted onto the liver surface of immunodeficient mice.
RESULTS: Functional hiPSC-LTs were successfully generated by infusing day 8 precultured hiPSC-LOs into DLs. Perfusion with oxygenated medium containing artificial red blood cells suppressed cell death and promoted hepatic function of hiPSC-LTs by mimicking the physiological oxygen concentration found in the fetal liver. Notably, oxygenated hiPSC-LTs demonstrated improved engraftment in vivo, as evidenced by increased human albumin levels in recipient mouse serum compared with nonoxygenated controls.
CONCLUSIONS: The oxygenation system using DLs and artificial red blood cells effectively supported the generation of transplantable, functional hiPSC-LT. This culture strategy enhances both the enlargement and functionality of hiPSC-organoids and represents a promising step toward developing alternatives to conventional organ transplantation.