Regenerative medicine is a rapidly growing area that aims to create, repair and/or replace tissues and organs by using combinations of cells, biomaterials, and biologically active molecules. Although the molecular and genetic determinants of heart development and regeneration are very complex, significant advances in the understanding of events contributing to these processes have been made. In this session, pioneers and leaders in the field of developmental biology and regenerative medicine gathered to review progress, difficulties and highlight new trends and directions in this evolving field.
The epicardium and vessel formation
J M Perez-Pomares (Malaga, ES) reviewed the importance of coronary blood vessel development to late embryonic and adult heart function. The coronary vascular network develops in close association with the epicardium, i.e. the outer tissue layer of the heart. The origin of the epicardial tissue is the proepicardium, a mass of coelomic-derived tissue which spreads over the originally bare myocardium forming the primitive epicardium, which in turns undergoes an epithelial-to-mesenchymal transformation. This gives rise to a migratory population of mesenchymal cells that contain the cellular precursors of coronary blood vessels, including part of the endothelial, smooth muscle and fibrous progenitors. In vitro, a specific growth factor supplement (bFGF + VEGF) is needed to favour the high coronary angioblast density which is required for these cells to undergo early vasculogenesis. Hopefully, those cells can be used for heart repair.
Multiple stem cell populations contribute to the formation of the myocardium.
R R Markwald (Charleston, US) highlighted the contribution of developmental biology to the progress of regenerative medicine. After birth, intracardiac progenitor (stem) cells continue to add new myocardial cells but at levels insufficient to rapidly respond to injuries, resulting in many attempts to promote cardiac repair or regeneration by direct injection of adult stem cells. Using a single cell engraftment model, he identified a population of circulating cells that reproducibly engrafts into cardiac tissues under control conditions and following surgical induction of myocardial infarction. Evaluation of the transdifferentiation potential of engrafted cells suggested that haematopoietic stem cells do not transdifferentiate into cardiomyocytes, endothelial cells or smooth muscle cells but, rather, fibroblastic cells. Of interest, periostin, a fasciclin gene, is highly upregulated in those cells. Based on experiments in periostin null mice, he proposed that periostin is pro-fibrogenic and anti-regenerative. In experimental MI, fibrous scar formation is reduced in periostin null mice. These provocative findings may affect our attitude toward current approaches for heart regeneration.
Stem cells and the engineered cardiac valve.
M H Yacoub (Harefield, GB) described the cells and extracellular matrix that are essential in order to construct a heart valve. The choice of cells to populate the tissue engineered valve is critical. Autologous, allogenic and possibly xenogenic stem and progenitor cells are being considered as candidates. These cells are compared before and after specific manipulations to the native valve cells with regard to both phenotype and function. Another feature which is essential for producing an “off the shelf” product, is the capacity of the valve to survive in the long term without being rejected, preferably without the use of non-specific immunosuppression. Currently, mesenchymal stem cells obtained from different sources are being investigated to meet the stringent criteria outlined above.
Myocardial Repair with tissue engineering
W-H Zimmermann (Hamburg, DE) described the creation of engineered heart muscle to repair infarcted myocardium in rodents. Construction of various tissue geometries is possible to accommodate a specific “therapeutic” demand. Embryonic stem cells can be used to construct engineered heart muscle. In addition, he addressed issues regarding the allocation of autologous cells for cardiac tissue engineering. However, these promising experiments need to be repeated in bigger animals before this approach could be considered in our clinical practice.