Evidence map›Paper›PMID 26188080›Full record

ArticleCryobiology2015

Machine perfusion enhances hepatocyte isolation yields from ischemic livers.

Maria-Louisa Izamis, Sinem Perk, Candice Calhoun, Korkut Uygun, Martin L Yarmush, François Berthiaume

Abstract readEvaluation Study
In one paragraph

Article in Cryobiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Clinical Hepatocyte Transplantation: What Is Next?Current transplantation reports · 2017
    Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 1 country.

Maria-Louisa IzamisCenter for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Hospital, 51 Blossom Street, Boston, MA 02114, United States. Electronic address: mizamis@mgh.harvard.edu.
Sinem PerkCenter for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Hospital, 51 Blossom Street, Boston, MA 02114, United States. Electronic address: perksin@gmail.com.
Candice CalhounCenter for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Hospital, 51 Blossom Street, Boston, MA 02114, United States. Electronic address: Calhoun.ck@gmail.com.
Korkut UygunCenter for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Hospital, 51 Blossom Street, Boston, MA 02114, United States. Electronic address: uygun.korkut@mgh.harvard.edu.
Martin L YarmushCenter for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Hospital, 51 Blossom Street, Boston, MA 02114, United States; Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, United States. Electronic address: ireis@sbi.org.
François BerthiaumeDepartment of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, United States. Electronic address: fberthia@rci.rutgers.edu.
Massachusetts General Hospital · USShriners Hospitals for Children - Erie · USHarvard University · USRutgers, The State University of New Jersey · US

Funding

Metabolic Modeling for Cadaveric Organ ResuscitationR01DK096075 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI UYGUN, KORKUT, YEH, HEIDI · 2012 to 2022
$3.9M
Metabolic Engineering for Improved Liver FunctionR01DK059766 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI YARMUSH, MARTIN L · 2002 to 2011
$3.5M
Computer-aided Development of a Liver Organ Culture SystemR00DK080942 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI UYGUN, KORKUT · 2010 to 2012
$900k
Use of Discarded Organs for Preparation of Liver GraftsR00DK088962 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI UYGUN, BASAK ELIF · 2014 to 2016
$844k
NIDDK NIH HHS R00 DK080942NIDDK NIH HHS R00DK088962NIDDK NIH HHS R01 DK059766NIDDK NIH HHS R01 DK096075NIDDK NIH HHS R01DK096075NIDDK NIH HHS R01DK59766
6 · The paper itself

Abstract

backgroundHigh-quality human hepatocytes form the basis of drug safety and efficacy tests, cell-based therapies, and bridge-to-transplantation devices. Presently the only supply of cells derives from an inadequate pool of suboptimal disqualified donor livers. Here we evaluated whether machine perfusion could ameliorate ischemic injury that many of these livers experience prior to hepatocyte isolation.

methodsNon-heparinized female Lewis rat livers were exposed to an hour of warm ischemia (34°C) and then perfused for 3h. Five different perfusion conditions that utilized the cell isolation apparatus were investigated, namely: (1) modified Williams Medium E and (2) Lifor, both with active oxygenation (95%O(2)/5%CO(2)), as well as (3) Lifor passively oxygenated with ambient air (21%O(2)/0.04%CO(2)), all at ambient temperatures (20 ± 2°C). At hypothermic temperatures (5 ± 1°C) and under passive oxygenation were (4) University of Wisconsin solution (UW) and (5) Vasosol. Negative and positive control groups comprised livers that had ischemia (WI) and livers that did not (Fresh) prior to cell isolation, respectively.

resultsFresh livers yielded 32 ± 9 million cells/g liver while an hour of ischemia reduced the cell yield to 1.6 ± 0.6 million cells/g liver. Oxygenated Williams Medium E and Lifor recovered yields of 39 ± 11 and 31 ± 2.3 million cells/g liver, respectively. The passively oxygenated groups produced 15 ± 7 (Lifor), 13 ± 7 (Vasosol), and 10 ± 6 (UW)million cells/g liver. Oxygenated Williams Medium E was most effective at sustaining pH values, avoiding the accumulation of lactate, minimizing edematous weight gain and producing bile during perfusion.

conclusionsMachine perfusion results in a dramatic increase in cell yields from livers that have had up to an hour of warm ischemia, but perfusate choice significantly impacts the extent of recovery. Oxygenated Williams Medium E at room temperature is superior to Lifor, UW and Vasosol, largely facilitated by its high oxygen content and low viscosity.

Indexed as

AdenosineAllopurinolAnimalsCell HypoxiaCell SeparationFemaleGlutathioneHepatocytesInsulinLiverOrgan Preservation SolutionsPerfusionRaffinoseRatsRats, Inbred LewTissue DonorsAdenosineAllopurinolGlutathioneInsulinOrgan Preservation SolutionsRaffinoseUniversity of Wisconsin-lactobionate solutionHepatocytesIsolationLiforPerfusionTemperatureUWVasosolViscosityWilliams E

Identifiers

PMID26188080
PMCPMC4584189
OpenAlexW2188512455

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.