CORDIS
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CORDIS

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A Functional, Mature In vivo Human Ventricular Muscle Patch for Cardiomyopathy

Project information

Grant agreement ID: 743225

Status

Ongoing project

  • Start date

    1 December 2017

  • End date

    30 November 2022

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 149 227,50

  • EU contribution

    € 2 149 227,50

Hosted by:

KAROLINSKA INSTITUTET

Sweden

Objective

Developing new therapeutic strategies for heart regeneration is a major goal for cardiac biology and medicine. While cardiomyocytes can be generated from human pluripotent stem (hPSC) cells in vitro, it has proven difficult to use these cells to generate a large scale, mature human heart ventricular muscle graft on the injured heart in vivo. The central objective of this proposal is to optimize the generation of a large-scale pure, fully functional human ventricular muscle patch in vivo through the self-assembly of purified human ventricular progenitors and the localized expression of defined paracrine factors that drive their expansion, differentiation, vascularization, matrix formation, and maturation. Recently, we have found that purified hPSC-derived ventricular progenitors (HVPs) can self-assemble in vivo on the epicardial surface into a 3D vascularized, and functional ventricular patch with its own extracellular matrix via a cell autonomous pathway. A two-step protocol and FACS purification of HVP receptors can generate billions of pure HVPs- The current proposal will lead to the identification of defined paracrine pathways to enhance the survival, grafting/implantation, expansion, differentiation, matrix formation, vascularization and maturation of the graft in vivo. We will captalize on our unique HVP system and our novel modRNA technology to deliver therapeutic strategies by using the in vivo human ventricular muscle to model in vivo arrhythmogenic cardiomyopathy, and optimize the ability of the graft to compensate for the massive loss of functional muscle during ischemic cardiomyopathy and post-myocardial infarction. The studies will lead to new in vivo chimeric models of human cardiac disease and an experimental paradigm to optimize organ-on-organ cardiac tissue engineers of an in vivo, functional mature ventricular patch for cardiomyopathy

Host institution

KAROLINSKA INSTITUTET

Address

Nobels Vag 5
17177 Stockholm

Sweden

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 2 149 227,50

Beneficiaries (1)

KAROLINSKA INSTITUTET

Sweden

EU Contribution

€ 2 149 227,50

Project information

Grant agreement ID: 743225

Status

Ongoing project

  • Start date

    1 December 2017

  • End date

    30 November 2022

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 149 227,50

  • EU contribution

    € 2 149 227,50

Hosted by:

KAROLINSKA INSTITUTET

Sweden