d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

WORKPACKAGE 8PROGENITOR CELLS FOR BIO-ARTIFICIAL LIVER

StemCellSystems

WP1Clinical,

application scenarios

WP3 Sensor development

WP6 Instrumentation

platforms

WP9 Dissemination, training and exploitation plans

WP10 Consortium Management

WP4 Microfluidics, packaging and

integration

WP2 System design and medical device

regulatory requirements

WP1Evaluation

LPMS Evaluation

Bioartificial Liver

Evaluation

WP8 Progenitor cells for bio-artificial liver

WP7 Communications,

patient management and decision support

WP5 Development and monitoring of

cell-based Liver Support Unit

Partners: UNEW, Charité, SCS, FhG-IBMTDevelop a cell source for use in bioreactors for the treatment of patients with for e.g. decompensating liver disease.

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

Drivers for WP8 approach

Stem cell-derived hepatocytes are expensive and have low functionality.

Develop a human equivalent of the rat B-13 cell line.

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

Drivers for WP8 approach

Stem cell-derived hepatocytes are expensive and have low functionality – seed-LIVER web site http://www.d-liver.eu/

human iPSC approach

B-13 approach= 6,000,000

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

Drivers for WP8 approach

Develop a human equivalent of the rat B-13 cell line.

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

Drivers for WP8 approach

Develop a human equivalent of the rat B-13 cell line.

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d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

Drivers for WP8 approach

Develop a human equivalent of the rat B-13 cell line

Utility (e.g. in toxicity assays)PhospholipidosisSteatosisDrug toxicity studiesGenotoxicity (phase I activated - )Genotoxicity studies (phase II activated)

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

Drivers for WP8 approach

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

H-13s – prototype human B-13 cells

Isolated progenitor cells from human pancreas – + glucocorticoid, hepatocyte-like cells, but tissue access too limited.

Focussed on a human acinar cell line that showed similar responses as B-13 cells to glucocorticoids.

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

H-13s – prototype human B-13 cells

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

H-13s – prototype human B-13 cells

AdV mediated gene expression of certain genes increases hepatic phenotype of HPACs after treatment with DEX

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

H-13s – prototype human B-13 cells

Piggybac stable transfection system chosen to provide a cost-effective means to enhance hepatic phenotype in HPAC cells

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

H-13s – prototype human B-13 cells

DEX-inducible transgene system designed

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

H-13s – prototype human B-13 cells

H-13 (HPAC with DEX-inducible expression of hHNF4α):marked up-regulation of hepatic gene expression

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

H-xx – additional prototype human B-13 cells

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

Summary – prototype human B-13 cells

• H-13 and H-14 cells – currently being more fully analysed

• H-13 and H-14 cells – functionality in bioreactors (Charite/SCS/Fraunhofer)

• Patent application

• Early commercial development - In vitro toxicity testing

d-LIVER Showcase Workshop,

Humanitas Milano, May 2015

Acknowledgements

The d-LIVER project is partly funded by the European Commission (Contract No. 287596)

www.d-liver.eu

StemCellSystems