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Therapy of primary and metastatic liver cancer by human iPS cell‐derived myeloid cells producing interferon‐β
Author(s) -
Sakisaka Masataka,
Haruta Miwa,
Komohara Yoshihiro,
Umemoto Satoshi,
Matsumura Keiko,
Ikeda Tokunori,
Takeya Motohiro,
Inomata Yukihiro,
Nishimura Yasuharu,
Senju Satoru
Publication year - 2017
Publication title -
journal of hepato‐biliary‐pancreatic sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 1868-6974
DOI - 10.1002/jhbp.422
Subject(s) - liver cancer , medicine , hepatocellular carcinoma , metastasis , interferon , cancer research , cancer cell , induced pluripotent stem cell , cancer , spleen , therapeutic effect , immunology , biology , biochemistry , embryonic stem cell , gene
Background iPS ‐ ML are myeloid lineage cells with a proliferative capacity derived from induced pluripotent stem ( iPS ) cells. This study aimed to examine therapeutic effect of iPS ‐ ML producing interferon‐β ( iPS ‐ ML / IFN ‐β) towards primary and metastatic liver cancer and investigate the mechanism of that effect. Methods We established a xenograft model of liver metastasis by injecting the spleen of SCID mice with MKN ‐45 human gastric cancer cells and also a primary liver cancer model by injecting SK ‐ HEP ‐1 human hepatocellular carcinoma cells into the liver. After cancer lesions were established, iPS ‐ ML / IFN ‐β was administered by intraperitoneal injection, and therapeutic effect was evaluated. Results The i.p. injection of iPS ‐ ML / IFN ‐β resulted in a significant retardation of cancer progression and prolonged mouse survival. The infiltration of i.p. administered iPS ‐ ML into tumor lesions located below the liver capsule was observed, suggesting tumor‐directed migration and penetration of the liver capsule by iPS ‐ ML . The IFN ‐β concentration in the liver was maintained at levels sufficient to exert an anti‐cancer effect for at least 3 days post‐injection, accounting for the potent therapeutic effect obtained by injection two to three times per week. Conclusions This study demonstrates the therapeutic potential of the iPS ‐ ML / IFN ‐β in patients with liver cancer.