Division of Cardiovascular Diseases Strategic Plan

Goals in Enabling Technologies and Methodologies for Cardiovascular Disease

1.7. Identify, characterize, and apply progenitor cells appropriate for cardiovascular regeneration and repair

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Overview

In recent years, a revolution has taken place in the field of CV regenerative medicine. The perception that the heart is incapable of self-renewal has been replaced by the view that cardiac cells can be replaced by resident and/or nonresident progenitor cells, but that the capacity for repair is overwhelmed by insults such as MI. This has led to a large number of clinical trials to test the safety and efficacy of different cell populations for treating acute MI and chronic heart failure, with only a modest degree of success in improving wall motion to date.The basic biology of cells that can contribute to CV repair is poorly understood, the cells have generally been incompletely characterized, and the cell fate and mechanisms of action are also unclear. Gender, age, and disease state can also have profound influences on stem cell function. This goal seeks to develop a sound evidence-based approach to cell transplantation for the treatment of CV diseases.

Strategies to Accomplish this Goal May Entail:

Basic Research:

  • Generate cardiac cell fate maps, and approaches to identify, purify, renew, and direct the differentiation of specific lineages of interest.
  • Facilitate partnerships and collaboration between developmental biologists and translational CV researchers to capitalize on recent progress in developmental biology research.
  • Develop and validate models of cell fate determination that can predict responses to perturbation.
  • Identify phenotypic markers, and develop lineages from embryonic stem cells and induced pluripotent stem cells.
  • Develop and validate imaging techniques for cell tracking.
  • Study the immunogenicity of allogeneic cells and strategies to overcome immune barriers.

Translational Research:

  • Translate findings in vitro and in small animal models into clinically relevant large animal models of CV disease.
  • Employ progenitor cells for tissue engineering. For example, engineer small-diameter blood vessels for coronary artery bypass grafting.
  • Develop scaffold materials for use in cell therapy to enhance cell survival and differentiation.

Clinical Research:

  • Apply the knowledge obtained in basic and preclinical studies to design better evidence-based clinical trials. For example, optimize the timing and delivery route for progenitor cells for treatment of acute MI.
  • Test well-characterized progenitor cells in clinical trials. For example, employ optimized progenitor cells capable of survival and differentiation to cardiomyocytes and vascular components for treatment of heart failure.

Resources:

  • Generate publicly available molecular, epigenetic, and functional databases on specific embryonic stem cell lines, induced pluripotent cells, and heart progenitor lineages.
  • Generate publicly available repositories of progenitor cells for CV cell therapy.

Contributing Sources:

September 2008

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