Proteomic analysis of cerebrospinal fluid of amyotrophic lateral sclerosis patients in the presence of autologous bone marrow derived mesenchymal stem cells

Author:

Reis Ana Luiza Guimarães1,Maximino Jessica Ruivo1,Lage Luis Alberto de Padua Covas2,Gomes Hélio Rodrigues2,Pereira Juliana2,Brofman Paulo Roberto Slud3,Senegaglia Alexandra Cristina3,Rebelatto Carmen Lúcia Kuniyoshi3,Daga Debora Regina3,Paiva Wellingson Silva2,Palmisano Giuseppe4,Chadi Gerson1

Affiliation:

1. FMUSP: Universidade de Sao Paulo Faculdade de Medicina

2. USP HC: Universidade de Sao Paulo Hospital das Clinicas

3. PUCPR: Pontificia Universidade Catolica do Parana

4. USP ICB: Universidade de Sao Paulo Instituto de Ciencias Biomedicas

Abstract

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal and fast progressive motoneuron degenerative disorder. There are still no drugs capable to slower disease evolution or to improve life quality of ALS patients. In that scenario, the cell therapy has emerged as an alternative to be investigated in clinical ALS. Method Taking the advantage of Proteomics and Protein-Protein Interaction Network analyses combined to bioinformatics, possible cellular mechanisms and molecular targets related to mesenchymal stem cells (MSC, 1x106 cells/kg, intrathecally in the lumbar region of the spine) were investigated in cerebrospinal fluid (CSF) of ALS patients who received intrathecal infusions of autologous bone marrow-derived MSC thirty days after cell therapy. Results Proteomics showed 220 deregulated proteins in CSF of ALS subjects. Bioinformatic enriched analyses evidenced APOA1, APOE, APP, C4A, C5, FGA, FGB, FGG and PLG, as highlighted targets as well as extracellular matrix and cell adhesion molecules as possible mechanisms related to the presence of MSC in CSF of ALS subjects. Conclusions We have demonstrated a possible role of extracellular matrix/cell adhesion molecules and their related highlighted targets to the presence of autologous MSC in CSF ALS patients. Trial Registration: Clinicaltrial.gov identifier NCT0291768. Registered 28 September 2016.

Publisher

Research Square Platform LLC

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