Liver micro-organs transcribe albumin and clotting factors and increase survival of 92% hepatectomized rats.
OBJECTIVE
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 microm 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.
Grad-Itach
Etty
E
Epigenesis Ltd, P.O. Box 45010, Jerusalem 91450, Israel.
Fuchs
Alicia Graciela
AG
Lev
Haya
H
Kotok
Tatyana
T
Shemesh
Ronen
R
Shouval
Daniel
D
Ilan
Yaron
Y
Mitrani
Eduardo
E
D000418:Albumins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001779:Blood Coagulation Factors / Q000235:genetics / Q000378:metabolism*; D046508:Culture Techniques; D004210:Dissection; D004867:Equipment Design; D006498:Hepatectomy / Q000401:mortality; D008099:Liver / Q000378:metabolism* / Q000601:surgery*; D019164:Liver, Artificial; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013534:Survival; D013997:Time Factors; D014158:Transcription, Genetic
D000418:Albumins; D001779:Blood Coagulation Factors