Perspectives on Directions and Priorities for Future Preclinical Studies in Regenerative Medicine

Lilian Grigorian Shamagian, Rosalinda Madonna, Doris Taylor, Andreu M. Climent, Felipe Prosper, Luis Bras-Rosario, Antoni Bayes-Genis, Péter Ferdinandy, Francisco Fernández-Avilés, Juan Carlos Izpisua Belmonte, Valentin Fuster, Roberto Bolli

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations


The myocardium consists of numerous cell types embedded in organized layers of ECM (extracellular matrix) and requires an intricate network of blood and lymphatic vessels and nerves to provide nutrients and electrical coupling to the cells. Although much of the focus has been on cardiomyocytes, these cells make up <40% of cells within a healthy adult heart. Therefore, repairing or regenerating cardiac tissue by merely reconstituting cardiomyocytes is a simplistic and ineffective approach. In fact, when an injury occurs, cardiac tissue organization is disrupted at the level of the cells, the tissue architecture, and the coordinated interaction among the cells. Thus, reconstitution of a functional tissue must reestablish electrical and mechanical communication between cardiomyocytes and restore their surrounding environment. It is also essential to restore distinctive myocardial features, such as vascular patency and pump function. In this article, we review the current status, challenges, and future priorities in cardiac regenerative or reparative medicine. In the first part, we provide an overview of our current understanding of heart repair and comment on the main contributors and mechanisms involved in innate regeneration. A brief section is dedicated to the novel concept of rejuvenation or regeneration, which we think may impact future development in the field. The last section describes regenerative therapies, where the most advanced and disruptive strategies used for myocardial repair are discussed. Our recommendations for priority areas in studies of cardiac regeneration or repair are summarized in Tables 1 and 2.

Original languageEnglish
Pages (from-to)938-951
Number of pages14
JournalCirculation Research
Issue number6
StatePublished - 15 Mar 2019


  • Preclinical research
  • Regeneration
  • Rejuvenation
  • Repair


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