Human Hepatocytes Isolated from Explanted Livers: A Powerful Tool to Understand End-stage Liver Disease and Drug Screening

Figures & data

Figure 1. Isolated cells obtained from diseased explanted livers can be used to mimic the in vivo environment and become an effective experimental model to study a number of liver diseases including ALD, NAFLD, NASH, and metabolic diseases.

Table 1. Patient’s demographic data, yield and viability of isolated hepatocytes

DISEASE	AGE	GENDER	VIABILITY%	ATTACHMENT EFFICIENCY%
PA	2	Female	78	80
PA	12 MO	Male	86	95
PA	20	Male	80	90
CRYPTO CIRRH	61	Female	80	90
CRYPTO CIRRH	72	Male	87	90
A1ATD	53	Female	70	80
A1ATD	59	Male	72	70
A1ATD	51	Male	85	90
CPS1	12 MO	Female	81	100
Alegille Syndrome	12 MO	Female	78	90
MSUD	17 MO	Male	85	95
OTC	21	Female	82	95
Control Liver	15	Male	88	98
Control Liver	11	Male	89	95
NASH	71	Male	81	90
NASH	71	Female	70	80
NASH	46	Male	82	90
NASH	54	Female	80	80
NASH	64	Male	80	70
NASH	62	Female	80	90
NASH	70	Male	80	90
NASH	62	Female	64	80
NASH	67	Female	75	80
ALD	48	Male	71	75
ALD	42	Male	75	80
ALD	52	Female	91	90
ALD	48	Male	88	85
ALD	42	Female	82	80
ALD	54	Male	80	90
ALD	60	Male	85	90

*PA: Propionic Acidemia; CRYPTO CIRRH: Cryptogenic cirrhosis; A1ATD: Alpha-1-antitrypsin deficiency; CPS1: Carbamoyl phosphate synthetase-1; MSUD: Maple syrup urine disease; OCT: Ornithine Transcarbamylase; NASH: nonalcoholic Steatohepatitis; ALD: Alcoholic Liver Disease.

Figure 2. (a) Example of NASH liver explant, (partial segments 2,3, Child-Pugh score C) before cell isolation; ongoing liver damage causing significant disruption of the normal hepatic architecture; surface of affected liver becomes irregular and nodular, with a progression of fibrosis. Representative phase-contrast images of cultured hepatocytes from NASH (b), MSUD (c), and ALD (d) livers, 24 hr culture. (e) Phase-contrast image of hepatocytes isolated from an ALD liver, recovered from cryopreservation, 24 h culture.

Figure 3. Detection of CYP3A4 and CYP2C9 gene induction in patient-derived hepatocytes isolated from 9 different diseased or cirrhotic explanted livers (PA, ALD, Crypto and NASH). CP: Child-Pugh.