Defatting heptocytes under flow

Joshua Yarmush, Gabriel Yarmush, Nir Nativ, Francois Berthiaume

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

There is a critical shortage of transplantable livers in both the US and the world. One method to increase the donor pool is to develop methodology to recondition extended criteria donor grafts, a large portion of which are moderate to severe macrosteatotic livers. Transplantation of these livers often leads to primary nonfunction caused by an increased susceptibility to the effects of ischemia reperfusion injury that result from the harvesting, transportation, and transplantation of the liver. Our lab has developed a novel cocktail of defatting reagents that can, over a period of two days, render hepatocytes lean and with good cell viability and function. Despite this accomplishment, in order to be feasibly performed in a clinical setting, the defatting process must be completed in a matter of hours. The current project focuses on understanding the differences between defatting in a static versus flow environment and then using this information to develop the ideal parameters for defatting whole organs. Our hypothesis in the current work is that using flow and the appropriate defatting agents, steatotic hepatocytes can be defatted in a clinically relevant time of hours, without decreasing cell viability or function. In order to test this hypothesis, a perfusion reactor was constructed which holds microscope slides that can be seeded with fatty hepatocytes. Perfusion of defatting media was performed at different flow rates over a six hour period. Results showed that within a six hour period, significant defatting (as compared to static cultures) was observed at both 2.0 and 4.0 ml/min as indicated by oil red O staining. Current experiments are focused on further evaluation of hepatocyte viability and function (e.g. albumin, urea, and cytochrome P450 function). These types of parametric experiments will form the basis for future perfusions with whole organs from obese rats.

Original languageEnglish (US)
Title of host publicationProceedings - 2014 40th Annual Northeast Bioengineering Conference, NEBEC 2014
PublisherInstitute of Electrical and Electronics Engineers Inc.
ISBN (Electronic)9781479937288
DOIs
StatePublished - Dec 2 2014
Event2014 40th Annual Northeast Bioengineering Conference, NEBEC 2014 - Boston, United States
Duration: Apr 25 2014Apr 27 2014

Publication series

NameProceedings of the IEEE Annual Northeast Bioengineering Conference, NEBEC
Volume2014-December
ISSN (Print)1071-121X
ISSN (Electronic)2160-7001

Other

Other2014 40th Annual Northeast Bioengineering Conference, NEBEC 2014
Country/TerritoryUnited States
CityBoston
Period4/25/144/27/14

All Science Journal Classification (ASJC) codes

  • Bioengineering

Keywords

  • Defatting
  • Flow device
  • Hepatocytes
  • Liver function
  • Macrosteatosis

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