NHLBI Working Group

Bio-Artificial Heart

Executive Summary


Introduction

The National Heart, Lung, and Blood Institute (NHLBI) convened a working group of experts on bioengineering, stem cells, biomaterials, biomechanics, cell therapies, and tissue regeneration and vascularization on May 23, 2013 at Rockledge II in Bethesda, Maryland. The purpose of the working group was to review the state of the science and to advise the NHLBI on new research directions needed to make progress towards the development of completely biological, preferably autologous replacement (i.e., "bio-artificial") hearts which would address the shortcomings of mechanical circulatory support devices.

Discussion, Challenges, and Key Questions:

While mechanical circulatory support devices have become one of the primary therapies for treating advanced heart failure, heart transplantation is a preferred treatment due to the lower mortality and morbidity associated with the therapy. However, heart transplantation has limited use due to the restricted availability of approximately 2000 donor hearts in the United States per year. Ventricular assist devices (VADs), while more reliable, smaller, and more biocompatible than earlier generations, require anticoagulation, and still present substantial risks for infection, stroke, and other adverse events. Considering the limitations to current therapies, and some of the progress made in the field of tissue engineering over the past decade, some researchers have turned their attention to creating fully functional, tissue-engineered (i.e., bio-artificial) replacement hearts.

The working group reviewed and discussed (1) the current state of work on bio-artificial hearts, (2) the use of stem cells in cardiac regeneration, (3) biomaterials, vascularization, and biomechanics in cardiac regeneration and bio-artificial hearts, and (4) clinical trials in cardiac regeneration and endpoints in cell therapy trials. Following the discussions, the working group acknowledged and reached consensus on the substantial number of significant challenges for development of a bio-artificial heart. These included:

  1. The need for cost-effective autologous and allogeneic sources of various cell types (e.g., cardiovascular, parenchymal) which enable the large-scale production of cells at the necessary density and purity.
  2. The need for sources of sterile, non-immunogenic, matrices that are optimized to provide the physical structure and functional characteristics of the heart wall. Such matrices should allow endothelialization, cell-seeding of the various cell phenotypes, appropriate cardiac electrical conduction, and be durable under the chronic contractile loads expected to be produced by a normally functioning heart.
  3. Determining methods to allow cells to mature and to survive in structures of sufficient thickness for acceptable function of the various types of cardiac tissues.

Questions that the working group raised during the discussion were:

  1. What are the near-term translational targets and what can be learned from current clinical approaches?
  2. What is the required three-dimensional (3D) structure for a bio-artificial heart?
  3. What are the oxygen diffusivity and nutrient demands for 3D heart development?
  4. How do myocytes chemically and mechanically couple to the scaffold?
  5. How does the matrix behave over time and what are the mechanical performance indices at the tissue level?
  6. What are the minimal functional requirements of the bio-artificial heart?
  7. Can progenitor cells be used for vascularization, how can they be conditioned, and how can endothelialization be improved?
  8. What are specifications for the cells, tissues, and complete organ?

Following the identification of challenges and questions to be answered, the working group reached consensus on the following recommendations, listed in priority order.

Recommendations:

  • Develop safe and reliable sources of biomaterials that provide structure, and sterility, in an attempt to meet the needs of heart regeneration, and facilitate adequate function of a bio-artificial heart.
  • Develop scalable technologies for generating large numbers of functional cells for use in a bio-artificial heart.
  • Develop in-silico models to facilitate development of a bio-artificial heart. The model should simulate processes (e.g., contraction and transport) and include means of evaluating structure (e.g., scaffold design).
  • Develop bioreactors and devices that provide for long term sterile delivery, maintenance, maturation, and transport of matrix and cells for use in bio-artificial hearts.
  • Define and develop (as needed) in vivo and in vitro assays and functional metrics for bio-artificial hearts.

Publication Plans:

A manuscript is planned for publication in a peer-reviewed journal.

NHLBI Contact:

J. Timothy Baldwin, Ph.D., NHLBI, NIH
baldwint@nhlbi.nih.gov

Publication Plans:

A manuscript is planned for publication in a peer-reviewed journal.

Working Group Members:

Chair: Anthony J. Atala, MD, Wake Forest University School of Medicine

Members:

  • Arnold I. Caplan, Ph.D., Case Western Reserve University
  • Karen L. Christman, Ph.D., University of California, San Diego
  • Gordon M. Keller, Ph.D., Ontario Cancer Institute
  • Harald C. Ott, M.D., Massachusetts General Hospital
  • Amit N. Patel, M.D., University of Utah
  • Michael S. Sacks, Ph.D., University of Texas
  • Doris A. Taylor, Ph.D., Texas Heart Institute
  • Jay H. Traverse, M.D., University of Minnesota

NHLBI Program Staff

  • Catherine D. Burke, M.A.
  • Denis B. Buxton, Ph.D.
  • Jonathan R. Kaltman, M.D.
  • Albert Lee, Ph.D.
  • Martha S. Lundberg, Ph.D.
  • Monica R. Shah, M.D.

Last Updated: Aug 2013




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