Critical factors in vitrification-based cryopreservation of precision-cut liver slices

PhD ceremony: Ms. N. Guan, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Critical factors in vitrification-based cryopreservation of precision-cut liver slices

Promotor(s): prof. G.M.M. Groothuis

Faculty: Mathematics and Natural Sciences

Precision-cut liver slices (PCLS) are widely used as an in vitro model in research including pharmacology and ADME/T (Absorption, Distribution, Metabolism and Elimination /Toxicology) of drugs. The research presented in the thesis of Na Guan aims to understand the critical steps of vitrification-based cryopreservation of precision-cut liver slices, with the ultimate goal of using this knowledge for the development of successful cryopreservation methods for PCTS (precision-cut tissue slices) to facilitate building of a tissue slice bank.

PCLS can be prepared from human and animal tissue and until now can only be used freshly after preparation. Successful cryopreservation of PCLS would allow the creation of a tissue bank from various species, decrease the use of laboratory animal use and facilitate the use of human PCLS in research. However, the viability of cryopreserved PCLS was not consistently good for all species and the critical factors involved in cryopreservation of PCLS have not been studied. Furthermore, Na Guan evaluated different viability and functionality endpoints for both overall responses and responses of the different liver cell types (hepatocytes, Kupffer cells, endothelial cells and stellate cells) within slices. Moreover, the research presented in her thesis explored the mechanism of chilling injury, the main obstacle for successful vitrification, at the gene expression level in the integrated tissue for the first time under the condition that damage from other injury events was minimized. The methods and results presented in Na Guans thesis provide important information towards the successful development of improved cryopreservation protocols for human organ or tissue slices, which is the ultimate aim of the research.