MSACL 2020 US Abstract

Self-Classified Topic Area(s): Proteomics

Spatio Temporal Proteomic Guided by MALDI MSI Opens the Door of Therapy for Spinal Cord Injury

Michel Salzet
Université de Lille, Inserm, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), F-59000 Lille, France

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Michel Salzet (Presenter)
Université De Lille, Inserm U1192

Presenter Bio: Professor Michel salzet (Distinguish Professor) Is a member of the Institut Universitaire de France in the speciality of immunoproteomic. He is director of the unit, UMR 1192 Inserm. He discovered with Professor Xavier Roucou, the ghost proteins through proteomic approaches combined with Bioinformatic analyses. For this achievement, they received the Quebec science Award for the discovery of the year 2014. Professor Michel Salzet has (co-)authored more than 335 papers (H-index 58, google scholar) and he has published in Top notch journals like Cancer Cells, Nature protocols, Nature Immunology, Circulation, Blood, Trends in immunology

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Abstract

Introduction:
Spinal cord injury (SCI) belongs to currently incurable disorders of the CNS and is accompanied by permanent health consequences-disability. In order to mimic a SCI, a balloon-compressive technique was used at thoracic Th8-9 spinal level in adult rat.

Methods:
4D MALDI Imaging, lipidomics, Saptio tempral tissue microproteomics were undertaken combined with confocal imaging. Exsosomes from Stem Cells, functionalized biomaterial, Rho A inhibitor have been tested in pre-clinical way to develop a smart biomaterial.

Results:
We determined the spatio-temporal events occurring in acute phase after SCI. Caudal segment has clearly been detected as the therapeutic target. We then assessed in a rat SCI model the in vivo impact of a sustained RhoA inhibitor administered in situ via functionalized-alginate scaffold. In order to decipher the underlying molecular mechanisms involved in such a process, an in vitro neuroproteomic-systems biology platform was developed in which the pan-proteomic profile of the dorsal root ganglia (DRG) cell line ND7/23 DRG was assessed in a large array of culture conditions using RhoAi and/or conditioned media obtained from SCI ex-vivo derived spinal cord slices. A fine mapping of the spatio-temporal molecular events of the RhoAi treatment in SCI was performed. The data obtained allow a better understanding of regeneration induced above and below the lesion site.

Conclusions:
Results notably showed a time-dependent alteration of the transcription factors profile along with the synthesis of growth cone-related factors (receptors, ligands, and signaling pathways) in RhoAi treated DRG cells and involvement of IgG by binding to their receptors on the DRG cells

Novel Aspect:
We established a novel origin of IgG, their role in neurites outgrowth modulation, and developed a smart biomaterial for treating SCI. We confirm that bone marrow stem cells can be use as therapeutic agents as demonstrated in dogs.