Perspectives on Directions and Priorities for Future Preclinical Studies in Regenerative Medicine
Grigorian Shamagian L (1,2), Madonna R (3,4), Taylor D (5), Climent AM (1,2), Prosper F (6), Bras-Rosario L (7), Bayes-Genis A (2,8), Ferdinandy P (9,10), Fernández-Avilés F (1,2), Izpisua Belmonte JC (11), Fuster V (2,12,13), Bolli R (14).
(1) From the Hospital Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain (L.G.S., A.M.C., F.F.-A.).
(2) CIBERCV, ISCIII, Madrid, Spain (L.G.S., A.M.C., A.B.-G., F.F.-A., V.F.).
(3) Center of Aging Sciences and Translational Medicine (CESI-MeT), Institute of Cardiology, G. d'Annunzio University, Chieti, Italy (R.M.).
(4) Department of Internal Medicine, the University of Texas Health Science Center at Houston (R.M., ).
(5) Texas Heart Institute, Houston (D.T.).
(6) Clinica Universidad de Navarra, Pamplona, Spain (F.P.).
(7) Cardiology Department, Santa Maria University Hospital (CHLN), Lisbon Academic Medical Centre and Cardiovascular Centre of the University of Lisbon, Faculty of Medicine, Portugal (L.B.-R.).
(8) Hospital Germans Trias i Pujol, Badalona, Spain (A.B.-G.)
(9) Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary (P.F.).
(10) Pharmahungary Group, Szeged, Hungary (P.F.).
(11) Salk Institute for Biological Studies, La Jolla (J.C.I.B.).
(12) The Mount Sinai Hospital, New York, NY (V.F.).
(13) Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (V.F.).
(14) University of Louisville (R.B.).
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 .
CITATION Circ Res. 2019 Mar 15;124(6):938-951. doi: 10.1161/CIRCRESAHA.118.313795