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A Proinflammatory Secretome Mediates the Impaired Immunopotency of Human Mesenchymal Stromal Cells in Elderly Patients with Atherosclerosis
- Source :
- Stem Cells Translational Medicine
- Publication Year :
- 2017
- Publisher :
- Oxford University Press (OUP), 2017.
-
Abstract
- Inflammation plays a pivotal role in the initiation and progression of atherosclerosis (ATH). Due to their potent immunomodulatory properties, mesenchymal stromal cells (MSCs) are evaluated as therapeutic tools in ATH and other chronic inflammatory disorders. Aging reduces MSCs immunopotency potentially limiting their therapeutic utility. The mechanisms that mediate the effect of age on MSCs immune-regulatory function remain elusive and are the focus of this study. Human adipose tissue-derived MSCs were isolated from patients undergoing coronary artery bypass graft surgery. MSCs:CD4+T-cell suppression, a readout of MSCs’ immunopotency, was assessed in allogeneic coculture systems. MSCs from elderly subjects were found to exhibit a diminished capacity to suppress the proliferation of activated T cells. Soluble factors and, to a lesser extent, direct cell-cell contact mechanisms mediated the MSCs:T-cell suppression. Elderly MSCs exhibited a pro-inflammatory secretome with increased levels of interleukin-6 (IL-6), IL-8/CXCL8, and monocyte chemoattractant protein-1 (MCP-1/CCL2). Neutralization of these factors enhanced the immunomodulatory function of elderly MSCs. In summary, our data reveal that in contrast to young MSCs, MSCs from elderly individuals with ATH secrete high levels of IL-6, IL-8/CXCL8 and MCP-1/CCL2 which mediate their reduced immunopotency. Consequently, strategies aimed at targeting pro-inflammatory cytokines/chemokines produced by MSCs could enhance the efficacy of autologous cell-based therapies in the elderly.
- Subjects :
- Adult
CD4-Positive T-Lymphocytes
0301 basic medicine
Aging
Chemokine
Mesenchymal stromal cells
Inflammation
CCL2
Proinflammatory cytokine
Immunopotency
03 medical and health sciences
Translational Research Articles and Reviews
medicine
Humans
Interleukin 8
Cells, Cultured
Chemokine CCL2
Aged
biology
Interleukin-6
business.industry
Monocyte
Interleukin-8
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
General Medicine
Middle Aged
Atherosclerosis
Coculture Techniques
030104 developmental biology
medicine.anatomical_structure
Immunology
biology.protein
medicine.symptom
Stem cell
business
Tissue‐Specific Progenitor and Stem Cells
Developmental Biology
Subjects
Details
- ISSN :
- 21576580 and 21576564
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Stem Cells Translational Medicine
- Accession number :
- edsair.doi.dedup.....2a98aaeb76393b476e4525e751785c7f
- Full Text :
- https://doi.org/10.1002/sctm.16-0221