title: Endomyocardial biopsy derived adherent proliferating cells - a potential cell source for cardiac tissue engineering.
abstract: Heart diseases are a leading cause of morbidity and mortality. Cardiac stem cells (CSC) are considered as candidates for cardiac-directed cell therapies. However, clinical translation is hampered since their isolation and expansion is complex. We describe a population of human cardiac derived adherent proliferating (CAP) cells that can be reliably and efficiently isolated and expanded from endomyocardial biopsies (0.1 cm(3)). Growth kinetics revealed a mean cell doubling time of 49.9 h and a high number of 2.54 x 10(7) cells in passage 3. Microarray analysis directed at investigating the gene expression profile of human CAP cells demonstrated the absence of the hematopoietic cell markers CD34 and CD45, and of CD90, which is expressed on mesenchymal stem cells (MSC) and fibroblasts. These data were confirmed by flow cytometry analysis. CAP cells could not be differentiated into adipocytes, osteoblasts, chondrocytes, or myoblasts, demonstrating the absence of multilineage potential. Moreover, despite the expression of heart muscle markers like alpha-sarcomeric actin and cardiac myosin, CAP cells cannot be differentiated into cardiomyocytes. Regarding functionality, CAP cells were especially positive for many genes involved in angiogenesis like angiopoietin-1, VEGF, KDR, and neuropilins. Globally, principal component and hierarchical clustering analysis and comparison with microarray data from many undifferentiated and differentiated reference cell types, revealed a unique identity of CAP cells. In conclusion, we have identified a unique cardiac tissue derived cell type that can be isolated and expanded from endomyocardial biopsies and which presents a potential cell source for cardiac repair. Results indicate that these cells rather support angiogenesis than cardiomyocyte differentiation.
authors.affiliation: Tissue Engineering Laboratory, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Tucholskystr. 2, 10117 Berlin, Germany. marion-renate.haag@charite.de
authors.forename: Marion
authors.initials: M
authors.lastname: Haag
authors.forename: Sophie
authors.initials: S
authors.lastname: Van Linthout
authors.forename: Sebastian E A
authors.initials: SE
authors.lastname: Schröder
authors.forename: Undine
authors.initials: U
authors.lastname: Freymann
authors.forename: Jochen
authors.initials: J
authors.lastname: Ringe
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
authors.forename: Michael
authors.initials: M
authors.lastname: Sittinger
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology; D023822:Tissue Engineering / Q000379:methods*