Primary Human Liver Cells as Source for Modular Extracorporeal Liver Support - a Preliminary Report

Abstract

Cell-based extracorporeal liver support is an option to assist or replace the failing organ until regeneration or until transplantation can be performed. The use of porcine cells or tumor cell lines is controversial. Primary human liver cells, obtained from explanted organs found to be unsuitable for transplantation, are a desirable cell source as they perform human metabolism and regulation. The Modular Extracorporeal Liver Support (MELS) concept combines different extracorporeal therapy units, tailored to suit the individual and intra-individual clinical needs of the patient. A multi-compartment bioreactor (CellModule) is loaded with human liver cells obtained by 5-step collagenase liver perfusion. A cell mass of 400 g – 600 g enables the clinical application of a liver lobe equivalent hybrid organ. A detoxification module enables single pass albumin-dialysis via a standard high-flux dialysis filter, and continuous venovenuous hemodiafiltration may be included if required. Cells from 54 human livers have been isolated (donor age: 56 ± 13 years, liver weight: 1862 ± 556 g resulting in a viability of 55.0 ± 15.9%). These grafts were not suitable for LTx, due to steatosis (54%), cirrhosis (15%), fibrosis (9%), and other reasons (22%). Out of 36 prepared bioreactors, 10 were clinically used to treat 8 patients with liver failure. The overall treatment time was 7–144 hours. No adverse events were observed. Initial clinical applications of the bioreactor evidenced the technical feasibility and safety of the system.

Problems and prospects of creation of extracorporal systems for support of functional livers status

“…Конструкция этого аппарата содержит биореактор, в котором афферентная жидкость перфузируется от центра к периферии, проходя через гепатоциты свиней (200-230 г), расположенные на полиэфирной матрице в специальном отсеке между двух слоев полиэфирных пластин [124]. Результаты I фазы клинических испытаний на семи пациентах с острой ПН показали улучшение неврологической симптоматики, снижение уровня аммиака и билирубина, отсутствие осложнений.…”

Bioartificial liver devices: Perspectives on the state of the art

“…Human hepatocytes are difficult to replicate in vitro, and daughter cells have not been shown to express sufficient levels of liver-specific functions [4,5]. One alternative is to use hepatocytes from other species.…”

First Report of Cryopreserved Human Hepatocytes Based Bioartificial Liver Successfully Used as a Bridge to Liver Transplantation

“…Sauer et al (14) reported their experience with a bioartificial liver device characterized by seeding and long-term cultivation of human hepatocytes immediately after isolation. That device is maintained viable for 21 days by continuous replacement and supplementation of cell culture media and could be used for clinical treatment if requested thereafter it should be discarded due to loss of function.…”