Networking & Grants
EPETER

Title: Cell Therapy Employing Endothelial Progenitors for Experimentally Induced Cardiac Ischemia, Acronym “EPETER

Duration: April 1st 2008 – March 31st 2010.

 

Founding source: European Union Frammework Programme 7 (FP7), People, Support for Training and Career Development of Researchers – Marie Curie International Reintegration Grants (IRG);

 

Grant Agreement No: 224888

 

Project director (reintegrated researcher): Dr. Marilena Lupu, Ph.D.

 

Coordinating institution: Institute of Cellular Biology and Pathology „Nicolae Simionescu“, Bucharest, Romania

 

Scientist in charge for supervising researcher’s reintegration: Dr. Maya Simionescu, Ph.D.

 

Project description:

The umbilical cord blood (UCB), Wharton’s jelly (WJ) and bone marrow (BM) are rich sources of self-renewing, multiple-lineage differentiating cells that have been recently proposed for tissue-specific cell replacement therapy. However, their ability to participate to cardiovascular tissue restoration has not been elucidated, yet. The project “Cell Therapy Employing Endothelial Progenitors for Experimentally Induced Cardiac Ischemia”, acronym “EPETER” aimed to isolation and characterization of endothelial progenitor cells (EPCs) from human BM, UCB and WJ for use in a novel experimental setting of cardiac ischemia.

 

During the first phase of the project, the ability of BM, UCB and WJ-derived stem cells to differentiate in endothelial lineage precursors in vitro, upon exposure to appropriate environmental signals, have been investigated. The results revealed that in long-term culture conditions with high serum concentrations and growth factor stimulation, UCB-derived cells showed the ability to robustly differentiate into adherent cells with epithelial-like features, as assessed by light and electron microscopy; in vitro angiogenic potential, represented by vascular tubes formation, correlated with the expression marker genes and proteins involved in EPCs proliferation, differentiation, chemotaxis, and survival. Under the same culturing conditions, WJ derived cells showed a mesenchymal stem (MSC) cell-like profile at phenotypic, gene and protein levels, with moderate expression of endothelial markers and multi-lineage differentiation potential. BM cells demonstrated modest patterns of endothelial marker expression.

 

During the second phase of the project, we employed a novel in vitro xenogeneic transplantation model to investigate the capacity of UCB-derived EPCs (UCB-EPCs) and WJ-derived MSC (WJ-MSC)-like cells to integrate intoboth living and ischemic cardiac tissue and to participate to neovascularization. The results revealed that UCB-EPCs integrated into the living cardiac tissue and contributed to vasculogenesis. Furthermore, in the same in vitro transplantation models, MSC-like cells were markedly chemoattracted towards both living and ischemic cardiac tissue and integrated robustly into the depth of the cardiac matrix, as assessed by immunohistochemical analyses using highly specific anti-human antibodies.

 

The results generated within this project have been synthesized in an original paper, which has been submitted to a high impact-journal and is currently under review process. More details regarding the methodologies used in this project and the obtained results will be provided on this webpage upon article publication. 

 

In conclusion, the functional ability of UCB- and WJ-derived progenitor cells to populate both living and ischemic cardiac tissue could be validated. The present study has brought new insights into stem cell biology field, advancing the development of feasible cellular therapies for cardiovascular tissue repair. Understanding the cardiac niche and microenvironmental interactions that regulate UCB-EPCs and WJ-MSC-like cells integration and neovascularization are essential for applying these cells to cardiovascular regeneration. Therefore, the research studies initiated within “EPETER” project will be further continued to depict the mechanisms of UCB-EPCs and WJ-MSC-like cells migration, integration, proliferation, maturation and survival into the cardiac tissue, in order to develop and optimize reliable cell replacement therapies for cardiovascular repair.

 

Project impact

“EPETER” has made significant contributions to impacts listed in the project work program, which relate to the (i) international scientific community via dissemination activities (oral and poster presentations to international conferences, publications), (ii) further development of researcher’s career (during “EPETER” project, the researcher has become the Scientific Coordinator, for her institution, of another FP7 grant, No. 245691, acronym “RAMSES”), (iii) public health (by raising the awareness of the public for cardiovascular diseases and by promoting translation of stem cell research findings “from bench to bedside”) and, not least, on the (iv) socio-economical development of the participating country and of the European Union by advancing research and technology, with a global impact on innovation.

 

For further details about “EPETER” project, please contact Marilena Lupu at the Institute of Cellular Biology and Pathology “Nicolae Simionescu”, 8 B.P. Hasdeu Str., 050568, Bucharest, Romania, by Tel.: +4021-319-4518, Fax: +4021-319-4519 or E-mail: marilena.lupu@icbp.ro