Cardiomyocytes Induce Endothelial Cells to Trans-Differentiate into Cardiac Muscle: Implications for Myocardium Regeneration

The concept of tissue-restricted differentiation of postnatal stem cells has been challenged by recent evidence showing pluripotency for hematopoietic, mesenchymal, and neural stem cells. Furthermore, rare but well documented examples exist of already differentiated cells in developing mammals that...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2001-09, Vol.98 (19), p.10733-10738
Main Authors: Condorelli, G., Borello, U., De Angelis, L., Latronico, M., Sirabella, D., Coletta, M., Galli, R., Balconi, G., Follenzi, A., Frati, G., M. G. Cusella De Angelis, Gioglio, L., Amuchastegui, S., Adorini, L., Naldini, L., Vescovi, A., Dejana, E., Cossu, G.
Format: Article
Language:English
Subjects:
Animals
Aorta - cytology
Biological Sciences
Cell Differentiation
Cell division
Cell lines
Cells, Cultured
Cellular differentiation
Embryonic stem cells
Endothelial cells
Endothelium, Vascular - cytology
Heart
Heart - physiology
Human umbilical vein endothelial cells
Humans
Mice
Muscular system
Myocardial Ischemia
Myocardium
Myocardium - cytology
Neural stem cells
Progenitor cells
Regeneration - physiology
Signal Transduction
Stem cells
Tissues
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The concept of tissue-restricted differentiation of postnatal stem cells has been challenged by recent evidence showing pluripotency for hematopoietic, mesenchymal, and neural stem cells. Furthermore, rare but well documented examples exist of already differentiated cells in developing mammals that change fate and trans-differentiate into another cell type. Here, we report that endothelial cells, either freshly isolated from embryonic vessels or established as homogenous cells in culture, differentiate into beating cardiomyocytes and express cardiac markers when cocultured with neonatal rat cardiomyocytes or when injected into postischemic adult mouse heart. Human umbilical vein endothelial cells also differentiate into cardiomyocytes under similar experimental conditions and transiently coexpress von Willebrand factor and sarcomeric myosin. In contrast, neural stem cells, which efficiently differentiate into skeletal muscle, differentiate into cardiomyocytes at a low rate. Fibroblast growth factor 2 and bone morphogenetic protein 4, which activate cardiac differentiation in embryonic cells, do not activate cardiogenesis in endothelial cells or stimulate trans-differentiation in coculture, suggesting that different signaling molecules are responsible for cardiac induction during embryogenesis and in successive periods of development. The fact that endothelial cells can generate cardiomyocytes sheds additional light on the plasticity of endothelial cells during development and opens perspectives for cell autologous replacement therapies.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.191217898