Authors:
Fitzpatrick, Emer; Wu, Yue; Dhadda, Paramjeet; Hughes, Robin D; Mitry, Ragai R; Qin, Hong; Lehec, Sharon C; Heaton, Nigel D; Dhawan, Anil
Summary:
Hepatocyte transplantation is becoming an accepted therapy for acute liver failure, either as a bridge to liver regeneration or to organ transplantation. Hepatocytes provide liver function in place of the failing organ. The maintenance of sufficient viability and function of the transplanted hepatocytes is a concern. There isrecent interest in mesenchymal stem cells (MSCs) for the provision of structural and trophic support tohepatocytes but few studies which use primary human hepatocytes. The aim of this study was to investigate if co-culture of human MSCs with cryopreserved human hepatocytes may improve their function and viability, thus with potential for cellular therapy of liver disease.
MSCs were isolated from human umbilical cordor adipose tissue and hepatocytes from donor organs unsuitable for transplantation. MSCs and hepatocytes were co-cultured in both direct and indirect contact. Conditioned medium (CM) from co-cultured MSCs and hepatocytes was also used on hepatocytes. Viability and liver-specific function were compared between test and controls.
Human hepatocytes which were co-cultured directly with MSCs demonstrated improved production of albumin from day 5 to day 25 of culture. This effect was most prominent at day 15 when albumin production in co-culture was 10x that of control monoculture. Likewise urea production was improved in co-culture from day 5 to 25. Indirect co-culture demonstrated improved albumin production by day 4 (1107ng/ml) versus hepatocyte monoculture (940ng/ml). Hepatocytes in CM demonstrated improved function but not to statistical significance. The viability of co-cultured hepatocytes was superior to that of monocultured cells with up to a 16% improvement.
Source:
Cell Transplantation; (10/18/13)