Human Hepatocyte Isolation for Liver Cell Therapy: Whole Marginal Livers or Healthy Segments from Splitting?

Abstract

We read with interest the article recently published in Transplantation by Mitry et al. (1). The authors reported their experience with human hepatocytes isolated from segment IV obtained from split-liver procedures and used the isolated liver cells for transplantation in a 1-day-old boy with antenatal diagnosis of ornithine transcarbamylase deficiency. The hepatocyte isolation procedure was carried out in three cases (in two cases the caudate lobe was also used) without affecting the outcome of the split-liver grafts transplanted into six patients. However, the authors do not state whether the right lobes (segment V to VIII) were transplanted into small-sized adult or large-sized pediatric recipients, nor the graft to recipient body weight ratio. The time (3 hr) required for ex-situ removal of segment IV might have jeopardized the quality of the graft, as several authors have reported better results for in situ than ex-situ split liver (2–3). Moreover, retaining segment IV with the right lobe graft could allow a greater hepatic volume for normal-sized adults without any problems related to the relative ischemia of the lateral part of segment IV (4). Regarding the isolation of human hepatocytes, according to our experience of routine use (almost 100 organs up to now) of marginal livers, deemed unusable for transplantation at harvesting (usually whole organs with macrosteatosis greater than 50%–60% but also several nonviral cirrhotic livers), for hepatocytes isolation we reported (5) an average cell yield of more than 7×106 hepatocytes per gram of liver tissue digested with a median viability of 73%±14%. Recently we improved our results in terms of viability achieving an average value of 80%±13% (unpublished data). The data from our experience using marginal livers are not different in terms of cell yield per gram of tissue digested (7×106 vs. 6.68×106) from those reported in the article by Mitry et al. (1), although we obtained a higher total number of hepatocytes (8×109 vs. 5.14×108). Median viability obtained by Mitry and collaborators was slightly higher (89%±8%) presumably due to the better quality of the liver tissue used. Although the use of segment IV, obtained from split-liver, for human hepatocytes isolation might increase the hepatic tissue available for research and for clinical liver cell therapy, the routine use of livers not usable for organ transplantation produced similar results in terms of cell yield and viability. Moreover, it might permit the development of large-scale tissue banking without risk of harming the outcome of recipients of whole organ or split-liver transplants. Umberto Baccarani Mauricio Sainz-Barriga Gian Luigi Adani Andrea Risaliti Fabrizio Bresadola Department of Surgery and Transplantation University Hospital Udine Udine, Italy Annibale Donini Division of Emergency and General Surgery Policlinico Monteluce Perugia Perugia, Italy Umberto Baccarani Andrea Sanna Fabrizio Bresadola Annibale Donini Bank of Human Hepatocytes University of Ferrara and Udine Ferrara and Udine, Italy