Transdifferentiation of Blood-Derived Human Adult Endothelial Progenitor Cells Into Functionally Active Cardiomyocytes
- 25 February 2003
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 107 (7), 1024-1032
- https://doi.org/10.1161/01.cir.0000051460.85800.bb
Abstract
Background— Further to promoting angiogenesis, cell therapy may be an approach for cardiac regeneration. Recent studies suggest that progenitor cells can transdifferentiate into other lineages. However, the transdifferentiation potential of endothelial progenitor cells (EPCs) is unknown. Methods and Results— EPCs were obtained from peripheral blood mononuclear cells of healthy adults or coronary artery disease (CAD) patients by cultivating with endothelial cell medium and growth factors. After 3 days, >95% of adherent cells were functionally and phenotypically EPCs. Diacetylated LDL–labeled EPCs were then cocultivated with rat cardiomyocytes for 6 days, resulting in significant increases of EPC cell length and size to a cardiomyocyte-like morphology. Biochemically, 9.94±1.39% and 5.04±1.09% of EPCs from healthy adults (n=15) or CAD patients (n=14, P Conclusions— EPCs from healthy volunteers and CAD patients can transdifferentiate in vitro into functionally active cardiomyocytes when cocultivated with rat cardiomyocytes. Cell-to-cell contact but not cellular fusion mediates EPC transdifferentiation. The therapeutic use of autologous EPCs may aid cardiomyocyte regeneration in patients with ischemic heart disease.Keywords
This publication has 20 references indexed in Scilit:
- Changing potency by spontaneous fusionNature, 2002
- Fas receptor signaling inhibits glycogen synthase kinase 3β and induces cardiac hypertrophy following pressure overloadJCI Insight, 2002
- Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytesJCI Insight, 2001
- HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathwayJCI Insight, 2001
- Selection of ventricular‐like cardiomyocytes from ES cellsin vitroThe FASEB Journal, 2000
- Blood-derived angioblasts accelerate blood-flow restoration in diabetic miceJCI Insight, 2000
- Transplanted cord blood–derived endothelial precursor cells augment postnatal neovascularizationJCI Insight, 2000
- Transplantation ofex vivoexpanded endothelial progenitor cells for therapeutic neovascularizationProceedings of the National Academy of Sciences of the United States of America, 2000
- Dystrophin expression in the mdx mouse restored by stem cell transplantationNature, 1999
- Cardiomyocytes can be generated from marrow stromal cells in vitroJCI Insight, 1999