Dataset Information

Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic and 1 degenerative intervertebral discs: A proteomic analysis

ABSTRACT: Mesenchymal stromal cells (MSCs) have been introduced as promising cell source for regenerative medicine. Besides their multilineage differentiation capacity, MSCs release a wide spectrum of bioactive factors. This secretome holds immunomodulatory and regenerative capacities. In intervertebral disc (IVD) cells, application of MSC secretome has been shown to decrease the apoptosis rate, induce proliferation and promote production of extracellular matrix (ECM). For clinical translation of secretome-based treatment, characterization of the secretome composition is needed to better understand the induced biological processes and identify potentially effective secretomes. Methods: This study aimed to investigate the proteome released by bone marrow derived MSCs following exposure to a healthy, traumatic, or degenerative human IVD environment by mass spectroscopy and quantitative immunoassay analyses. Exposure of MSCs to the proinflammatory stimulus interleukin 1β (IL-1b) was used as control.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Witold Wolski

LAB HEAD: Sibylle Grad

PROVIDER: PXD021281 | Pride | 2021-09-09

REPOSITORIES: Pride

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Publications

Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis.

Wangler Sebastian S Kamali Amir A Wapp Christina C Wuertz-Kozak Karin K Häckel Sonja S Fortes Claudia C Benneker Lorin M LM Haglund Lisbet L Richards R Geoff RG Alini Mauro M Peroglio Marianna M Grad Sibylle S

Stem cell research & therapy 20210107 1

<h4>Background</h4>Mesenchymal stromal cells (MSCs) have been introduced as promising cell source for regenerative medicine. Besides their multilineage differentiation capacity, MSCs release a wide spectrum of bioactive factors. This secretome holds immunomodulatory and regenerative capacities. In intervertebral disc (IVD) cells, application of MSC secretome has been shown to decrease the apoptosis rate, induce proliferation, and promote production of extracellular matrix (ECM). For clinical tra ...[more]

PMID: 33413584

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Project description:Canine adipose-derived mesenchymal stem cells (cAD-MSCs) show therapeutic promise for their regenerative potential, particularly in their secretome. However, concerns arise regarding the impact of in vitro cultivation need for storing therapeutic doses, prompting this study to comprehensively explore the impact of in vitro aging on gene expression and secretome composition. The study involved collecting abdominal adipose tissue samples from nine healthy female dogs, from which cAD-MSCs were extracted and cultured. Stem cells were validated through trilineage differentiation assays and flow cytometry immunophenotyping. Gene expression profiling, using RT-qPCR array and cAD-MSCs secretome LC-MS/MS analysis, were conducted at passages 3 and 6 to reveal gene expression and protein composition alterations during in vitro culture. Gene expression profiling of in vitro aged cAD-MSCs revealed expression alterations, while significant downregulation was observed in two MSC-associated genes. Proteomic analysis revealed 10% distinctively expressed proteins, and several up- and downregulations. Grouping these proteins with biologically significant ones, Gene Ontology Panther Pathway analysis revealed that P3 proteins were significantly associated with cytoskeletal regulation, nicotinic acetylcholine receptor signaling, inflammation mediated by chemokine and cytokine signaling, Wnt signaling, and CCKR signaling map. In contrast, P6 proteins were linked to the xanthine and guanine salvage pathway, adenine and hypoxanthine salvage pathway, and blood coagulation pathway. To the best of our knowledge, this study presents the first original perspective on the changes in secretome composition that occur when cAD-MSCs age in vitro. Our findings highlight significant changes that, in conclusion, indicate the regenerative potential of cAD-MSCs and that their secretome may be compromised due to in vitro aging. Consequently, our study suggests a preference for earlier passages when considering these cells for therapeutic applications.

Dataset Information

Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic and 1 degenerative intervertebral discs: A proteomic analysis

Publications

Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis.

Similar Datasets

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