SCIENTIFIC REPORtS | (2018) 8:3418 | DOI:10.1038/s41598-018-21757-4
InForm software: a semi-
automated research tool to
identify presumptive human
hepatic progenitor cells, and other
histological features of pathological
Anne S. Kramer
, Bruce Latham
, Luke A. Diepeveen
, Lingjun Mou
, Georey J. Laurent
, Laura Ochoa-Callejero
& George C. Yeoh
Hepatic progenitor cells (HPCs) play an important regenerative role in acute and chronic liver
pathologies. Liver disease research often necessitates the grading of disease severity, and pathologists’
reports are the current gold-standard for assessment. However, it is often impractical to recruit
pathologists in large cohort studies. In this study we utilise PerkinElmer’s “InForm” software package
to semi-automate the scoring of patient liver biopsies, and compare outputs to a pathologist’s
assessment. We examined a cohort of eleven acute hepatitis samples and three non-alcoholic fatty liver
disease (NAFLD) samples, stained with HPC markers (GCTM-5 and Pan Cytokeratin), an inammatory
marker (CD45), Sirius Red to detect collagen and haematoxylin/eosin for general histology. InForm
was congured to identify presumptive HPCs, CD45
inammatory cells, areas of necrosis, fat and
collagen deposition (p < 0.0001). Hepatitis samples were then evaluated both by a pathologist using
the Ishak-Knodell scoring system, and by InForm through customised algorithms. Necroinammation
as evaluated by a pathologist, correlated with InForm outputs (r
= 0.8192, p < 0.05). This study
demonstrates that the InForm software package provides a useful tool for liver disease research,
allowing rapid, and objective quantication of the presumptive HPCs and identies histological features
that assist with assessing liver disease severity, and potentially can facilitate diagnosis.
HPCs are a heterogeneous population, expressing immature and intermediate phenotypes of biliary and hepatic
. Histologically, they are small ovoid cells with a high nuclear-to-cytoplasmic ratio. ey are present
in the healthy liver at low abundance, residing in the liver stem cell niche termed the “canals of Hering”
phenotype and distribution of HPCs vary according the liver pathophysiology and severity, and known markers
including Pan Cytokeratin, CK19, NCAM and SOX-9 also stain cholangiocytes
. As such, the identication
of HPCs is challenging, and a reliable method which is capable of identifying and quantifying HPCs of varying
histological phenotypes is urgently required.
Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, The
University of Western Australia, Crawley, WA, Australia.
School of Molecular Sciences, The University of Western
Australia, Crawley, WA, Australia.
Centre for Cell Therapy and Regenerative Medicine, School of Biomedical
Sciences, The University of Western Australia, Crawley, WA, Australia.
PathWest Laboratory Medicine WA, Fiona
Stanley Hospital, Murdoch, WA, Australia.
WA Liver & Kidney Surgical Transplant Service, Sir Charles Gairdner
Hospital, Nedlands, Australia.
School of Pharmacy and Biomedical Science, Curtin Health Innovation Research
Institute, Curtin University, Bentley, WA, Australia.
Angiogenesis group, Oncology Area, Centre for Biomedical
Research of La Rioja, Logroño, Spain. Correspondence and requests for materials should be addressed to G.C.Y.
Received: 23 August 2017
Accepted: 30 January 2018
Published: xx xx xxxx