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Final Report Summary - EPETER (Cell therapy employing endotheliad progenitors for experimentally induced cardiac ischemia)

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' (EPETER) aimed to isolation and characterisation of endothelial progenitor cells (EPCs) from human UCB, WJ, and BM for use in a novel experimental setting of cardiac ischemia. The project has lead to the generation of original results with applications in regenerative medicine field. These results have been synthesised in two papers, already submitted for evaluation to the Journal of Cellular and Molecular Medicine (impact factor 5.1 manuscript ID: JCMM-05-2010-007) and Stem Cell Research (impact factor 3.3 manuscript ID: SCR-D-10-00044).

During the second phase of the project, we employed a novel in vitro transplantation model to investigate the capacity of UCB-derived EPCs (UCB-EPCs) and WJ-derived MSC (WJ-MSC)-like cells to integrate into living and ischemic murine embryonic ventricular slices and to participate to neovascularisation. The results revealed that green fluorescent protein-transfected UCB-EPCs generated vascular tube-like structures in direct contact with living, but not with ischemic ventricular slices, as also assessed by immunohistochemical staining with antibodies to human vWF, CD31, nuclei, and mitochondria; the soluble factors secreted by the living slices were not sufficient for vascular tube-like structures induction, as assessed in a trans-well coculture system. Furthermore, in the same in vitro transplantation models, MSC-like cells were markedly chemoattracted towards both vital and ischemic ventricular slices, and integrated robustly into the depth of the cardiac matrix, as assessed by immunohistochemical analyses using antibodies against pan-cadherin and human nuclei.

In conclusion, UCB-EPCs form vascular tube-like structures in contact with living cardiac tissue and the direct cell-to-cell interaction is a prerequisite in their induction. The functional ability of novel WJ-derived cells to populate both living and ischemic cardiac tissue could also be validated in vitro on murine ventricular tissue slices. Understanding the cardiac niche and microenvironmental interactions that regulate UCB-EPCs and WJ-MSC-like cells integration and neovascularisation 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 optimise reliable cell replacement therapies for cardiovascular regeneration.

The present study has brought new insights into stem cell biology field, advancing the development of feasible cellular therapies for cardiovascular tissue repair. 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 and national conferences, publications),
(ii) career development of the researcher (during EPETER project development, the reintegrated researcher has become a project director and a scientific coordinator, for her institution, of an international German-Romanian bilateral cooperation grant, No. MOE09/R51, acronym CORES, and a FP7 grant, No. 245691, acronym RAMSES, respectively),
(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').

For further details about EPETER, please see project web page at or contact Dr Marilena Lupu at the Institute of Cellular Biology and Pathology 'Nicolae Simionescu', 8 B.P. Hasdeu Str., 050568, Bucharest, Romania, Tel.: +4021-319-4518, Fax: +4021-319-4519, e-mail: