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.
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.
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.
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
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.