title: Biophysical cues enhance myogenesis of human adipose derived stem/stromal cells.
abstract: Adipose-derived stem/stromal cell (ASC)-based tissue engineered muscle grafts could provide an effective alternative therapy to autografts - which are limited by their availability - for the regeneration of damaged muscle. However, the current myogenic potential of ASCs is limited by their low differentiation efficiency into myoblasts. The aim of this study was to enhance the myogenic response of human ASCs to biochemical cues by providing biophysical stimuli (11% cyclic uniaxial strain, 0.5 Hz, 1h/day) to mimic the cues present in the native muscle microenvironment. ASCs elongated and fused upon induction with myogenic induction medium alone. Yet, their myogenic characteristics were significantly enhanced with the addition of biophysical stimulation; the nuclei per cell increased approximately 4.5-fold by day 21 in dynamic compared to static conditions (23.3 ± 7.3 vs. 5.2 ± 1.6, respectively), they aligned at almost 45° to the direction of strain, and exhibited significantly higher expression of myogenic proteins (desmin, myoD and myosin heavy chain). These results demonstrate that mimicking the biophysical cues inherent to the native muscle microenvironment in monolayer ASC cultures significantly improves their differentiation along the myogenic lineage.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Yilgor Huri
authors.forename: C A
authors.initials: CA
authors.lastname: Cook
authors.forename: D L
authors.initials: DL
authors.lastname: Hutton
authors.forename: B C
authors.initials: BC
authors.lastname: Goh
authors.forename: J M
authors.initials: JM
authors.lastname: Gimble
authors.forename: D J
authors.initials: DJ
authors.lastname: DiGirolamo
authors.forename: W L
authors.initials: WL
authors.lastname: Grayson
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods
keywords: Adipose-derived stem cell; Cyclic strain; Dynamic culture; Myogenesis; Skeletal muscle