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Liver regeneration and energetic changes in rats following hepatic radiation therapy and hepatocyte transplantation by 31 P MRSI
Author(s) -
Landis Charles S.,
Zhou Hongchao,
Liu Laibin,
Hetherington Hoby P.,
Guha Chandan
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12507
Subject(s) - hepatocyte , transplantation , medicine , radiation therapy , in vivo , cancer research , concomitant , endocrinology , chemistry , biology , in vitro , biochemistry , microbiology and biotechnology
Abstract Background & Aims Radiation‐induced liver damage ( RILD ) is a poorly understood and potentially devastating complication of hepatic radiation therapy ( RT ) for liver cancers. Previous work has demonstrated that hepatocyte transplantation ( HT ) can ameliorate RILD in rats. We hypothesized that RT inhibits generation of cellular ATP and suppresses hepatic regeneration. Methods To study the metabolic changes that occur in RILD with and without HT , 31 P MRSI data were acquired in rats treated with partial hepatectomy ( PH ) alone, PH with hepatic irradiation ( PHRT ) or PHRT with HT ( PHRT + HT ). Results Both [γ ‐ ATP ] and ATP /Pi 31 P MRSI signal ratio initially decreased and subsequently returned to baseline levels within 2 weeks after PH , which is consistent with other published data. Persistently reduced [γ‐ ATP ] and ATP /Pi 31 P MRSI signal ratio were observed in rats up to 20 weeks after PHRT . However, progressive increases in [γ ‐ ATP ] were observed over time in the group of rats receiving PHRT + HT . Normal [γ ‐ ATP ] was observed 20 weeks after PHRT + HT (vs. PH alone), although, ATP /Pi levels did not return to normal after PHRT + HT . Ex vivo histological studies were performed to confirm liver repopulation with transplanted hepatocytes and the amelioration of pathologic changes of RILD . Conclusions These findings suggest that 31 P MRSI can be used to monitor the progress of RILD and its amelioration using transplanted hepatocytes to simultaneously restore metabolic function while replacing host hepatocytes damaged by RT .