TY - JOUR
T1 - Liver micro-organs transcribe albumin and clotting factors and increase survival of 92% hepatectomized rats
AU - Grad-Itach, Etty
AU - Fuchs, Alicia Graciela
AU - Lev, Haya
AU - Kotok, Tatyana
AU - Shemesh, Ronen
AU - Shouval, Daniel
AU - Ilan, Yaron
AU - Mitrani, Eduardo
PY - 2003/10/1
Y1 - 2003/10/1
N2 - Background/Aims: Currently there is no effective non-surgical therapy for most patients with fulminant or end stage chronic liver disease. Methods: We have prepared rat liver micro-organs (LMOs), which preserve the liver micro-architecture and ensure that no cell is more than 150 μm away from a source of nutrients and gases. The function of LMOs has been evaluated in vitro and in a new extra-corporeal liver device termed aLIVE in which LMOs are exposed to liver-like hemodynamic conditions. Results: In vitro LMOs maintain normal physiological and biochemical functions including oxygen consumption, glucose metabolism, conversion of ammonia to urea, secretion of albumin and de novo transcription of genes coding for albumin and clotting factors. Inside the aLIVE bioreactor, LMOs also display sustained oxygen consumption, glucose metabolism and transcription of albumin and clotting factors IX and X, when connected both to normal and to 92% hepatectomized rats. Survival of 92% hepatectomized rats was 40% longer following a single 4-h treatment with aLIVE, compared to untreated animals. Conclusions: An extra-corporeal liver device, aLIVE, which provides key liver functions, has been developed. When tested in 92% hepatectomized rats, aLIVE improved the clinical condition and significantly increased survival time of the treated rats.
AB - Background/Aims: Currently there is no effective non-surgical therapy for most patients with fulminant or end stage chronic liver disease. Methods: We have prepared rat liver micro-organs (LMOs), which preserve the liver micro-architecture and ensure that no cell is more than 150 μm away from a source of nutrients and gases. The function of LMOs has been evaluated in vitro and in a new extra-corporeal liver device termed aLIVE in which LMOs are exposed to liver-like hemodynamic conditions. Results: In vitro LMOs maintain normal physiological and biochemical functions including oxygen consumption, glucose metabolism, conversion of ammonia to urea, secretion of albumin and de novo transcription of genes coding for albumin and clotting factors. Inside the aLIVE bioreactor, LMOs also display sustained oxygen consumption, glucose metabolism and transcription of albumin and clotting factors IX and X, when connected both to normal and to 92% hepatectomized rats. Survival of 92% hepatectomized rats was 40% longer following a single 4-h treatment with aLIVE, compared to untreated animals. Conclusions: An extra-corporeal liver device, aLIVE, which provides key liver functions, has been developed. When tested in 92% hepatectomized rats, aLIVE improved the clinical condition and significantly increased survival time of the treated rats.
KW - Albumin
KW - Artificial liver support
KW - Bioreactor
KW - Clotting factor
KW - Liver device
KW - Liver failure
UR - http://www.scopus.com/inward/record.url?scp=0141786772&partnerID=8YFLogxK
U2 - 10.1016/s0168-8278(03)00351-9
DO - 10.1016/s0168-8278(03)00351-9
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C2 - 12971965
AN - SCOPUS:0141786772
SN - 0168-8278
VL - 39
SP - 552
EP - 558
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -