title: Different Donors Mesenchymal Stromal Cells Secretomes Reveal Heterogeneous Profile of Relevance for Therapeutic Use.
abstract: Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by null mutations in the dystrophin gene. Although the primary defect is the deficiency of muscle dystrophin, secondary events, including chronic inflammation, fibrosis, and muscle regeneration failure are thought to actively contribute to disease progression. Despite several advances, there is still no effective therapy for DMD. Therefore, the potential regenerative capacities, and immune-privileged properties of mesenchymal stromal cells (MSCs), have been the focus of intense investigation in different animal models aiming the treatment of these disorders. However, these studies have shown different outcomes according to the sources from which MSCs were obtained, which raise the question whether stem cells from distinct sources have comparable clinical effects. Here, we analyzed the protein content of the secretome of MSCs, isolated from three different sources (adipose tissue, skeletal muscle, and uterine tubes), obtained from five donors and evaluated their in vitro properties when cocultured with DMD myoblasts. All MSC lineages showed pathways enrichment related to protein metabolic process, oxidation-reduction process, cell proliferation, and regulation of apoptosis. We found that MSCs secretome proteins and their effect in vitro vary significantly according to the tissue and donors, including opposite effects in apoptosis assay, indicating the importance of characterizing MSC secretome profile before its use in animal and clinical trials. Despite the individual differences a pool of conditioned media from all MSCs lineages was able to delay apoptosis and enhance migration when in contact with DMD myoblasts.
authors.affiliation: 1 Human Genome and Stem Cell Research Center, Institute of Biosciences University of São Paulo , São Paulo, Brazil .
authors.forename: Amanda
authors.initials: A
authors.lastname: Assoni
authors.affiliation: 1 Human Genome and Stem Cell Research Center, Institute of Biosciences University of São Paulo , São Paulo, Brazil .
authors.forename: Giuliana
authors.initials: G
authors.lastname: Coatti
authors.affiliation: 1 Human Genome and Stem Cell Research Center, Institute of Biosciences University of São Paulo , São Paulo, Brazil .
authors.forename: Marcos C
authors.initials: MC
authors.lastname: Valadares
authors.affiliation: 1 Human Genome and Stem Cell Research Center, Institute of Biosciences University of São Paulo , São Paulo, Brazil .
authors.forename: Melinda
authors.initials: M
authors.lastname: Beccari
authors.affiliation: 1 Human Genome and Stem Cell Research Center, Institute of Biosciences University of São Paulo , São Paulo, Brazil .
authors.forename: Juliana
authors.initials: J
authors.lastname: Gomes
authors.affiliation: 1 Human Genome and Stem Cell Research Center, Institute of Biosciences University of São Paulo , São Paulo, Brazil .
authors.forename: Mayra
authors.initials: M
authors.lastname: Pelatti
authors.affiliation: 1 Human Genome and Stem Cell Research Center, Institute of Biosciences University of São Paulo , São Paulo, Brazil .|2 Fleury Group (Research and Development Department), São Paulo, Brazil .
authors.forename: Miguel
authors.initials: M
authors.lastname: Mitne-Neto
authors.affiliation: 2 Fleury Group (Research and Development Department), São Paulo, Brazil .
authors.forename: Valdemir M
authors.initials: VM
authors.lastname: Carvalho
authors.affiliation: 1 Human Genome and Stem Cell Research Center, Institute of Biosciences University of São Paulo , São Paulo, Brazil .
authors.forename: Mayana
authors.initials: M
authors.lastname: Zatz
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology; D032446:Myoblasts / Q000187:drug effects / Q000473:pathology; D020543:Proteome / Q000378:metabolism*; D014019:Tissue Donors
chemical_list: D017077:Culture Media, Conditioned; D020543:Proteome
keywords: Duchenne muscular dystrophy; jagged 1; mesenchymal stromal cells; proteome; secretome