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Journal of Gastroenterology and Digestive Diseases | Volume 3
May 25-26, 2018 | New York, USA
World Liver Conference 2018
S
carcity of liver donors and difficulties in obtaining
functional primary human hepatocytes in clinically
relevant numbers poses immense challenge for liver
transplantation. This extrapolates to non-availability of
primary hepatocyte culture alternatives for drug induced
hepatotoxicity screening and studying hepatotropic
infections. Though iPSC-derived hepatocyte cells emerged
as alternatives, maturity of the differentiated state,
prominence of fetal metabolism, promiscuous differentiation
to related endoderm lineages and immune rejection poses
a roadblock for preclinical/clinical applications. Owing to
ease of expansion and established immune-evasiveness
of Mesenchymal stem cells (MSCs), an attempt is made to
trans-differentiate human adipose tissue derived MSCs to
hepatocytes using a combinationof developmentally relevant
transcriptional factors and hepatogenic cues. IMHeps so
derived manifested robust expression of liver enriched
transcription factors, metabolic signatures comparable
to human hepatocytes, drug inducible Cytochrome P450
enzyme activities mirroring adult hepatocytes and robust
xenobiotic clearance. IMHeps are permissive to hepatotropic
viruses certifying junctional maturity, a facet required for
viral entry. In-depth analysis of background Mesenchymal
memory in iMHeps indicated erasure of connective tissue
differentiation potential indicating stability of the hepatic
state even upon withdrawal of the initial hepatogenic cues
used for trans-differentiation. Though iMHeps have forgone
Mesenchymal differentiation abilities an unanticipated
conservation of immune-modulatory abilities, a hallmark
of native MSCs, was exhibited by iMHeps upon co-culture
with activated immune cells. IMHeps could thus emerge
as immune-compatible alternatives to primary human
hepatocytes and transformed hepatoma lines for studies on
drug induced hepatotoxicity, modelling liver infections and
as transplantable surrogates for liver failure.
Speaker Biography
S Jyothi Prasanna had completed her Doctoral studies from the prestigious Indian
Institute of Science, India. Her Doctoral Research involved studies on IFNγ signaling
in hepatocellular carcinomas and the relevance of downstream pathways in antiviral
immunity. As a Lead Scientist in Stem Cell Research Center, Manipal Hospital, she
was instrumental in developing preclinical models to test the efficacy of allogeneic
mesenchymal stem cells and has a patent on clinical scale expansion of human MSCs.
Currently, she is heading the Injury, Repair and Regeneration team as a Professor at
School of Regenerative Medicine, Manipal Academy of Higher Education..
e:
jyothi.prasanna@manipal.eduMesenchymal stem cell derived hepatocytes (iMHeps): Invaluable tools for predictive hepatotoxicity
and immune-compatible surrogates for liver function support
S Jyothi Prasanna
Manipal Academy of Higher Education, India