Hepatocyte Transplantation in an Acute Liver Failure Due to Mushroom Poisoning

Schneider, Andrea L.C.; Attaran, Masoumeh; Meier, P. N.; Strassburg, Christian P.; Manns, Michael P.; Ott, Michael; Barthold, Marc; Arseniev, Lubomir; Becker, Thomas; Panning, Bernd

doi:10.1097/01.tp.0000232451.93703.ab

Cited by 86 publications

(49 citation statements)

References 7 publications

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“…This supportive role of MSCs is particularly promising in the context of cell transplantation for acute liver failure (ALF). Hepatocyte transplantation alone may provide a bridge to either regeneration of the native liver or to transplantation, allowing sufficient time for an organ to become available (25,26,28). MSCs are a potential alternative to HC transplantation for ALF, as discussed.…”

Section: Improved Function Of Hepatocytes In Msc Coculturementioning

confidence: 99%

Coculture with Mesenchymal Stem Cells Results in Improved Viability and Function of Human Hepatocytes

Fitzpatrick

Dhadda

et al. 2015

Cell Transplant

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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 is a lot of recent interest in mesenchymal stem cells (MSCs) for the provision of structural and trophic support to hepatocytes, but few studies currently use primary human hepatocytes. The aim of this study was to investigate if coculture 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 cord or adipose tissue. Hepatocytes were isolated from donor organs unsuitable for transplantation. MSCs and hepatocytes were cocultured in both direct and indirect contact. Conditioned medium (CM) from cocultured MSCs and hepatocytes was also used on hepatocytes. Viability and liver-specific function were compared between test and controls. Human hepatocytes that were cocultured directly with MSCs demonstrated improved production of albumin from day 5 to day 25 of culture. This effect was most prominent at day 15. Likewise, urea production was improved in coculture from day 5 to 25. Indirect coculture demonstrated improved albumin production by day 4 (1,107 ng/ml) versus hepatocyte monoculture (940 ng/ml). Hepatocytes in CM demonstrated a nonsignificant improvement in function. The viability of cocultured hepatocytes was superior to that of monocultured cells with up to a 16% improvement. Thus, coculture of human hepatocytes with MSCs demonstrates both improved function and viability. The effect is seen mainly with direct coculture but can also be seen in indirect culture and with CM. Such coculture conditions may convey major advantages in hepatocyte survival and function for cell transplantation.

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Section: Improved Function Of Hepatocytes In Msc Coculturementioning

confidence: 99%

Coculture with Mesenchymal Stem Cells Results in Improved Viability and Function of Human Hepatocytes

Fitzpatrick

Dhadda

et al. 2015

Cell Transplant

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“…There have been attempts to use hepatocytes as substitutes to orthotopic liver transplantation to increase the availability of donor material [1]. For example, hepatocyte transplantations were used as a treatment for acute liver failure [2][3][4] and for some metabolic diseases in adults and children, such as urea cycle defects [5,6], glycogen storage disease types 1a and 1b [7,8], and CriglerNajjar syndrome type 1 [9,10]. Nevertheless, the metabolism of isolated hepatocytes somewhat differs to that within tissue.…”

Section: Introductionmentioning

confidence: 99%

DMSO modulates the pathway of apoptosis triggering

Banič¹,

Nipič²,

Šuput³

et al. 2011

Cellular and Molecular Biology Letters

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Abstract:We demonstrate here that distribution of caspase-9 influences the pathway of apoptosis triggering, since caspase-9 is activated efficiently only when it is distributed solely in the cytosol. Caspase-9 moves to the nuclei in a response to cell stress during isolation of primary hepatocytes; this is called preapoptotic cell stress response. The dimethyl sulfoxide (DMSO) treatment cannot prevent the migration of caspase-9 into the nuclei when it is added to primary hepatocytes immediately after isolation; however, it can trigger redistribution of caspase-9 from the nuclei into the cytosol when added 1 day post-isolation. This redistribution is temporary, since caspase-9 returns to the nuclei within 48 hours of DMSO treatment. Thereafter, some caspase-9 is retained in the nuclei of DMSO-treated hepatocytes for longer than in the nuclei of untreated hepatocytes. By measuring caspase activities, we demonstrate that the addition of DMSO to cell culture medium can temporarily normalize the susceptibility of hepatocytes for apoptosis triggering through the intrinsic pathway. DMSO contributes also to the prolonged pathway inactivation, i.e., by extending preapoptotic cell stress response. We propose that DMSO extends the survival of primary hepatocytes by modulating preapoptotic cell stress response, which could be exploited for extending the lifespan of other primary cell cultures.

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“…transplants in humans have been attempted by the use of human hepatocytes isolated from cadaveric livers. 41 However, donor organs are scarce, and the need for lifelong immunosuppressive therapy, as well as the heterogeneity of patients, lack of controls and follow-up duration, greatly limit this approach.…”

Section: Gpscs and Heart Regenerationmentioning

confidence: 99%