title: Thoracic aortas from multiorgan donors are suitable for obtaining resident angiogenic mesenchymal stromal cells.
abstract: 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 approximately 2.0 x 10(4) 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. Disclosure of potential conflicts of interest is found at the end of this article.
authors: Clinical Pathology, Policlinico S. Orsola, via Massarenti 9, 40138 Bologna, Italy. gianandr.pasquinelli@unibo.it
authors: Gianandrea
authors: G
authors: Pasquinelli
authors: Pier Luigi
authors: PL
authors: Tazzari
authors: Cristiana
authors: C
authors: Vaselli
authors: Laura
authors: L
authors: Foroni
authors: Marina
authors: M
authors: Buzzi
authors: Gianluca
authors: G
authors: Storci
authors: Francesco
authors: F
authors: Alviano
authors: Francesca
authors: F
authors: Ricci
authors: Massimiliano
authors: M
authors: Bonafè
authors: Catia
authors: C
authors: Orrico
authors: Gian Paolo
authors: GP
authors: Bagnara
authors: Andrea
authors: A
authors: Stella
authors: Roberto
authors: R
authors: Conte
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D001013:Aorta, Thoracic / Q000166:cytology*; D001808:Blood Vessels / Q000166:cytology*; D002454:Cell Differentiation; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology*; D014019:Tissue Donors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D042461:Vascular Endothelial Growth Factor A; D019009:Proto-Oncogene Proteins c-kit