title: Dynamic Support Culture of Murine Skeletal Muscle-Derived Stem Cells Improves Their Cardiogenic Potential In Vitro.
abstract: Ischemic heart disease is the main cause of death in western countries and its burden is increasing worldwide. It typically involves irreversible degeneration and loss of myocardial tissue leading to poor prognosis and fatal outcome. Autologous cells with the potential to regenerate damaged heart tissue would be an ideal source for cell therapeutic approaches. Here, we compared different methods of conditional culture for increasing the yield and cardiogenic potential of murine skeletal muscle-derived stem cells. A subpopulation of nonadherent cells was isolated from skeletal muscle by preplating and applying cell culture conditions differing in support of cluster formation. In contrast to static culture conditions, dynamic culture with or without previous hanging drop preculture led to significantly increased cluster diameters and the expression of cardiac specific markers on the protein and mRNA level. Whole-cell patch-clamp studies revealed similarities to pacemaker action potentials and responsiveness to cardiac specific pharmacological stimuli. This data indicates that skeletal muscle-derived stem cells are capable of adopting enhanced cardiac muscle cell-like properties by applying specific culture conditions. Choosing this route for the establishment of a sustainable, autologous source of cells for cardiac therapies holds the potential of being clinically more acceptable than transgenic manipulation of cells.
authors.affiliation: Department of Cardiothoracic Surgery, Heart Center, University of Cologne, 50937 Cologne, Germany ; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Neef
authors.affiliation: Department of Cardiothoracic Surgery, Heart Center, University of Cologne, 50937 Cologne, Germany ; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Treskes
authors.affiliation: Institute for Neurophysiology, University of Cologne, 50931 Cologne, Germany.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Cardiothoracic Surgery, Heart Center, University of Cologne, 50937 Cologne, Germany ; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Drey
authors.affiliation: Department of Cardiothoracic Surgery, Heart Center, University of Cologne, 50937 Cologne, Germany ; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
authors.forename: Sureshkumar Perumal
authors.initials: SP
authors.lastname: Srinivasan
authors.affiliation: Institute for Neurophysiology, University of Cologne, 50931 Cologne, Germany.
authors.forename: Tomo
authors.initials: T
authors.lastname: Saric
authors.affiliation: Institute for Neurophysiology, University of Cologne, 50931 Cologne, Germany.
authors.forename: Erastus
authors.initials: E
authors.lastname: Nembo
authors.affiliation: Institute for Neurophysiology, University of Cologne, 50931 Cologne, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Semmler
authors.affiliation: Institute for Neurophysiology, University of Cologne, 50931 Cologne, Germany.
authors.forename: Filomain
authors.initials: F
authors.lastname: Nguemo
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies, 13353 Berlin, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Stamm
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Cowan
authors.affiliation: Department of Cardiothoracic Surgery, Heart Center, University of Cologne, 50937 Cologne, Germany.
authors.forename: Antje-Christin
authors.initials: AC
authors.lastname: Deppe
authors.affiliation: Department of Cardiothoracic Surgery, Heart Center, University of Cologne, 50937 Cologne, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Scherner
authors.affiliation: Department of Cardiothoracic Surgery, Heart Center, University of Cologne, 50937 Cologne, Germany ; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wittwer
authors.affiliation: Institute for Neurophysiology, University of Cologne, 50931 Cologne, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.affiliation: Department of Cardiothoracic Surgery, Heart Center, University of Cologne, 50937 Cologne, Germany ; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wahlers
authors.affiliation: Department of Cardiothoracic Surgery, Heart Center, University of Cologne, 50937 Cologne, Germany ; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
authors.forename: Yeong-Hoon
authors.initials: YH
authors.lastname: Choi