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TISSUE-SPECIFIC STEM CELLS |
1 Clinical Pathology, Dept. of Experimental Pathology, Surgical Pathology, Dept. of Haematology, Oncology and Laboratory Medicine, Centre for Stem Cell Research, Policlinico S. Orsola, University of Bologna, Italy
2 Cardiovascular Tissue Bank, Dept. of Haematology, Oncology and Laboratory Medicine, Policlinico S. Orsola, University of Bologna, Italy
3 Vascular Surgery, Dept. of Cardiothoracic and Vascular Medicine, Policlinico S. Orsola, University of Bologna, Italy
4 C.R.B.A., Policlinico S. Orsola, University of Bologna, Italy
5 Department of Histology, Embryology and Applied Biology, Policlinico S. Orsola, University of Bologna, Italy
6 Clinical Pathology, Dept. of Experimental Pathology, Policlinico S. Orsola, University of Bologna, Italy
7 Department of Histology, Embryology and Applied Biology, Centre for Stem Cell Research, Policlinico S. Orsola, University of Bologna, Italy
* To whom correspondence should be addressed. E-mail: gianandr.pasquinelli{at}unibo.it.
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Abstract |
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The clinical use of endothelial progenitor cells is hampered by difficulties in obtaining an adequate number of functional progenitors. This study aimed to establish whether human thoracic aortas harvested from healthy multi-organ donors can be a valuable source of angiogenic progenitors.
Immunohistochemical tissue studies showed that two distinct cell populations with putative stem cell capabilities, one composed of CD34+ cells and the other of c-kit+ cells, are present in between the media and adventitia of human thoracic aortas. ki-67+ cells with high growth potential were located in an area corresponding to the site of CD34+ and c-kit+ cell residence. We thus isolated cells (0.5 
2.0 x 104 aortic progenitors/25 cm2) which, upon culturing, co-expressed molecules of mesenchymal stromal cells, i.e., CD44+, CD90+, CD105+ and showed a transcript expression of stem cell markers, e.g., OCT4, c-kit, BCRP-1, IL6, and BMI-1. Cell expansion was adequate for use in a clinical setting. A subset of cultured cells acquired the phenotype of endothelial cells in the presence of VEGF, e.g., increased expression of KDR and vWF positivity, as documented by flow cytometry, immunofluorescence, electron microscopy and RT-PCR assays. An in vitro angiogenesis test kit revealed that cells were able to form capillary-like structures within 6 hours of seeding.
This study demonstrates that thoracic aortas from multi-organ donors yield mesenchymal stromal cells with the ability to differentiate in vitro into endothelial cells. These cells can be used for the creation of an allogenic bank of angiogenic progenitors thus providing new options for restoring vascularization at ischemic sites.
Key Words. Mesenchymal Stromal Cells, Human thoracic aorta, Multi-organ donor, Angiogenesis, Allograft
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