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Comparison of Two Representative Methods for Differentiation of Human Induced Pluripotent Stem Cells into Mesenchymal Stromal Cells
Published on: October 20, 2023
The antiproliferative effect of mesenchymal stem cells is a fundamental property shared by all stromal cells
Simon Jones1, Nicole Horwood, Andrew Cope
1Department of Haematology, Division of Investigative Science, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, United Kingdom.
Abstract:
Although it has been widely demonstrated that human mesenchymal stem cells exert potent immunosuppressive effects, there is little information as to whether more mature mesenchymal stromal cells (SC) share the same property. Accordingly, we set out to test the ability of SC from different human tissues to inhibit the proliferation of PBMC following polyclonal stimuli. Chondrocytes, as well as fibroblasts from synovial joints, lung, and skin, were used as a source of SC. Irrespective of their differentiation potential and/or content of progenitor cells, SC from all tissues exhibited antiproliferative functions. This was in marked contrast to parenchymal cells. Although SC did not interfere with early T lymphocyte activation, they arrested stimulated T cells in the G(0)/G(1) phase of the cell cycle and rescued them from apoptosis. In addition, IFN-gamma and TNF-alpha production were reduced. We observed that the inhibitory effect is ultimately mediated by soluble factors, the production of which requires SC to be licensed in an inflammatory environment by cell contact. We conclude that the immunosuppressive effect of mesenchymal cells is not confined to multipotent stem cells, but is a fundamental characteristic of all stroma. Our data suggest that SC, appropriately licensed, regulate T cell homeostasis.
Insights
Mesenchymal stromal cells (SC) from various human tissues suppress T cell proliferation and reduce inflammatory cytokine production. This immunosuppressive function is a fundamental characteristic of all stroma, not limited to stem cells.
Area of Science:
- Immunology
- Cell Biology
- Regenerative Medicine
Background:
- Human mesenchymal stem cells are known for potent immunosuppressive effects.
- Limited data exists on whether more mature mesenchymal stromal cells (SC) possess similar properties.
Purpose of the Study:
- To investigate the immunosuppressive capacity of SC from diverse human tissues.
- To determine if SC inhibit peripheral blood mononuclear cell (PBMC) proliferation.
Main Methods:
- SC were isolated from chondrocytes and fibroblasts from synovial joints, lung, and skin.
- SC antiproliferative function was tested against polyclonal stimuli-activated PBMCs.
- T cell activation, cell cycle arrest, apoptosis, and cytokine production (IFN-gamma, TNF-alpha) were analyzed.
Main Results:
- SC from all tested tissues demonstrated significant antiproliferative effects on PBMCs.
- SC arrested stimulated T cells in the G(0)/G(1) phase and prevented apoptosis.
- IFN-gamma and TNF-alpha production were reduced, mediated by soluble factors requiring inflammatory licensing.
Conclusions:
- The immunosuppressive effect is a fundamental characteristic of all mesenchymal stroma, not exclusive to multipotent stem cells.
- Licensed SC play a role in regulating T cell homeostasis.
- These findings broaden the understanding of mesenchymal cell immunomodulatory functions.
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