Unraveling local tissue changes within severely injured skeletal muscles in response to MSC-based intervention using MALDI Imaging mass spectrometry

Scientific Reports
Oliver KleinSven Geißler

Abstract

Pre-clinical and clinical studies are now beginning to demonstrate the high potential of cell therapies in enhancing muscle regeneration. We previously demonstrated functional benefit after the transplantation of autologous bone marrow mesenchymal stromal cells (MSC-TX) into a severe muscle crush trauma model. Despite our increasing understanding of the molecular and cellular mechanisms underlying MSC's regenerative function, little is known about the local molecular alterations and their spatial distribution within the tissue after MSC-TX. Here, we used MALDI imaging mass spectrometry (MALDI-IMS) in combination with multivariate statistical strategies to uncover previously unknown peptide alterations within severely injured skeletal muscles. Our analysis revealed that very early molecular alterations in response to MSC-TX occur largely in the region adjacent to the trauma and only to a small extent in the actual trauma region. Using "bottom up" mass spectrometry, we subsequently identified the proteins corresponding to the differentially expressed peptide intensity distributions in the specific muscle regions and used immunohistochemistry to validate our results. These findings extend our current understanding about the early ...Continue Reading

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Citations

Jul 16, 2021·Nanoscale·Kristen N SikoraRichard W Vachet
Dec 12, 2019·Analytical Chemistry·Kristen N SikoraRichard W Vachet
Dec 7, 2021·Journal of Cachexia, Sarcopenia and Muscle·Cyriel Sebastiaan OlieVered Raz

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Methods Mentioned

BETA
electrophoresis
PCA

Software Mentioned

flexImaging
SCiLS
PLSA
MADLI
Mascot engine
ProteoWizard
SCiLS Lab
ImagePrep
flexAnalysis
flexControl

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