Partial hepatectomy and subsequent radiation facilitates engraftment of mouse embryonic stem cells in the liver |
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Authors: | Kobayashi N Ando M Kosaka Y Yong C Okitsu T Arata T Ikeda H Kobayashi K Ueda T Kurabayashi Y Tanaka N |
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Affiliation: | Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. immortal@md.okayama-u.ac.jp |
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Abstract: | For liver-targeted regenerative medicine, embryonic stem (ES) cell-derived hepatocyte-like cells proffer great expectation. In vitro exposure to a combination of various growth factors, such as hepatocyte growth factor and fibroblast growth factor-4, as well as cytokines, leads to differentiation of ES cells into hepatocyte-like cells. We sought to determine the in vivo environment that allowed engraftment of ES cells transplanted to the liver. Thus, we examined the effect of partial hepatectomy (50%) (PHT) and subsequent radiation (RT) of the male Balb/c mouse host liver on ES cell engraftment. ES cells (5 x 10(6)) derived from 129Sv mice were transplanted into the residual liver. The controls were ES cells transplanted into a normal liver. Bromo-deoxy-residine (BrdU)-uptake was performed to evaluate the effect of hepatectomy and RT on hepatocyte regeneration. Mouse ES cells engrafted, forming teratomas in the normal liver without showing any mononuclear infiltration. A liver modified by PHT and RT facilitated engraftment of mouse ES cells compared with a normal liver. Hepatic RT significantly suppressed hepatocytic uptake of BrdU. |
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