title: MALDI imaging mass spectrometry: discrimination of pathophysiological regions in traumatized skeletal muscle by characteristic peptide signatures.
abstract: Due to formation of fibrosis and the loss of contractile muscle tissue, severe muscle injuries often result in insufficient healing marked by a significant reduction of muscle force and motor activity. Our previous studies demonstrated that the local transplantation of mesenchymal stromal cells into an injured skeletal muscle of the rat improves the functional outcome of the healing process. Since, due to the lack of sufficient markers, the accurate discrimination of pathophysiological regions in injured skeletal muscle is inadequate, underlying mechanisms of the beneficial effects of mesenchymal stromal cell transplantation on primary trauma and trauma adjacent muscle area remain elusive. For discrimination of these pathophysiological regions, formalin-fixed injured skeletal muscle tissue was analyzed by MALDI imaging MS. By using two computational evaluation strategies, a supervised approach (ClinProTools) and unsupervised segmentation (SCiLS Lab), characteristic m/z species could be assigned to primary trauma and trauma adjacent muscle regions. Using "bottom-up" MS for protein identification and validation of results by immunohistochemistry, we could identify two proteins, skeletal muscle alpha actin and carbonic anhydrase III, which discriminate between the secondary damage on adjacent tissue and the primary traumatized muscle area. Our results underscore the high potential of MALDI imaging MS to describe the spatial characteristics of pathophysiological changes in muscle.
authors: Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany; Core Unit Proteomics, Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Oliver
authors: O
authors: Klein
authors: Kristin
authors: K
authors: Strohschein
authors: Grit
authors: G
authors: Nebrich
authors: Janina
authors: J
authors: Oetjen
authors: Dennis
authors: D
authors: Trede
authors: Herbert
authors: H
authors: Thiele
authors: Theodore
authors: T
authors: Alexandrov
authors: Patrick
authors: P
authors: Giavalisco
authors: Georg N
authors: GN
authors: Duda
authors: Philipp
authors: P
authors: von Roth
authors: Sven
authors: S
authors: Geissler
authors: Joachim
authors: J
authors: Klose
authors: Tobias
authors: T
authors: Winkler
mesh_terms: D000199:Actins / Q000032:analysis; D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000293:injuries* / Q000473:pathology*; D010455:Peptides / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D000199:Actins; D010455:Peptides
keywords: Digital histology; MALDI Imaging; Muscle injuries; Technology