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Reprogramming cell identity to develop new therapies against Inherited Metabolic Disorders of the liver

Reprogramming cell identity to develop new therapies against Inherited Metabolic Disorders of the liver

Objective

Liver diseases are becoming one of the most common causes of mortality in developing countries, and orthotopic liver transplantation is the only available treatment. However, this procedure carries implies indefinite immunosupression treatment associated with heavy side effects and eventual rejection. Furthermore, an increasing number of patients die while on the liver transplant waiting list due to the shortage of donor livers. Hepatocyte transplantation recently became an alternative to transplantation for the treatment of life-threatening Ineherithed Metabolic Diseases (IMDs) of the liver. However, this approach is also hampered by the lack of donors and by the difficulty in expending hepatocytes in vitro. Therefore, developing alternative source of hepatocytes represents a major challenge for the regenerative medicine field. Pluripotent stem cells generated from reprogrammed somatic cells (human Induced Pluripotent Stem Cells or hIPSCs) represent an advantageous solution since they can proliferate indefinitely in vitro while maintaining their capacity to differentiate into a broad number of cell types including hepatocytes. In addition, hIPSCs could enable the production of patient specific cells fully immuno-compatible with the original donor thereby avoiding the need for immune suppressive treatment. Here, we propose to systematically address the limitations preventing the use of hIPSCs for cells based therapy of IMDs. We will first develop novel methods to generate “better” hIPSCs fully compatible with clinical applications and to differentiate them into adult hepatocyes. In parallel, we will establish a novel approach for editing the mammalian genome and to correct the genetic defects associated with IMDs. Finally, we will validate the safety and the functionality of hIPSCs derived hepatocytes in vivo. Overall this comprehensive study will aim to provide the first proof of principle that hIPSCs could be useful in novel therapies against IMDs.
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Principal Investigator

Ludovic Patrick Vallier (Dr.)

Host institution

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

Address

Trinity Lane The Old Schools
Cb2 1tn Cambridge

United Kingdom

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 500 000

Principal Investigator

Ludovic Patrick Vallier (Dr.)

Administrative Contact

Renata Schaeffer (Ms.)

Beneficiaries (1)

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THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

United Kingdom

EU Contribution

€ 1 500 000

Project information

Grant agreement ID: 281335

Status

Closed project

  • Start date

    1 December 2012

  • End date

    30 November 2017

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 1 500 000

  • EU contribution

    € 1 500 000

Hosted by:

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

United Kingdom