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TRANSLATIONAL AND CLINICAL RESEARCH: MESENCHYMAL STEM CELLS SERIES |
aClinical Pathology, Department of Experimental Pathology,
bSurgical Pathology, Department of Haematology, Oncology and Laboratory Medicine,
cCardiovascular Tissue Bank, Department of Haematology, Oncology and Laboratory Medicine,
dVascular Surgery, Department of Cardiothoracic and Vascular Medicine,
eCentro Ricerca Biomedica Applicata,
fDepartment of Histology, Embryology and Applied Biology,
gCentre for Stem Cell Research, Policlinico S. Orsola, University of Bologna, Bologna, Italy
Key Words. Mesenchymal stromal cells • Human thoracic aorta • Multiorgan donor • Angiogenesis • Allograft
Correspondence: Gianandrea Pasquinelli, M.D., Clinical Pathology, Policlinico S. Orsola, via Massarenti 9, 40138 Bologna, Italy. Telephone: ++39516364288; Fax: ++3951306861; e-mail: gianandr.pasquinelli{at}unibo.it
Received November 15, 2006;
accepted for publication March 31, 2007.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS April 19, 2007.
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 multiorgan 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 per 25 cm2) which, upon culturing, coexpressed 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, Interleukin-6) 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 vascular endothelial growth factor (e.g., increased expression of KDR and von Willebrand factor positivity), as documented by flow cytometry, immunofluorescence, electron microscopy, and reverse transcription-polymerase chain reaction 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 multiorgan 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.
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