Human adipose tissue-derived mesenchymal stem cells induce explosive T-cell proliferation

Area of Science:

• Immunology
• Cell Biology
• Regenerative Medicine

Background:

• Mesenchymal stem cells (MSCs) are known to inhibit immune cell proliferation, primarily through anti-inflammatory factors.
• However, MSCs may also possess properties that activate resting immune cells, necessitating a deeper understanding for clinical use.

Purpose of the Study:

• To investigate the effect of human adipose tissue-derived MSCs on the activation, proliferation, and function of nonactivated peripheral blood mononuclear cells (PBMCs).
• To elucidate the behavior of MSCs under both inflammatory and noninflammatory conditions in relation to immune cell modulation.

Main Methods:

• Co-culturing human adipose-derived MSCs with autologous or allogeneic PBMCs in direct and transwell systems.
• Analyzing PBMC proliferation, gene expression of inflammatory mediators and growth factors in MSCs, and T-cell subset populations (CD4+, CD25+, CD127negFoxP3+).

Main Results:

• Co-culture with MSCs significantly increased PBMC proliferation (3-fold), with a further 25-fold increase observed after MSC removal.
• MSCs exhibited increased mRNA expression of pro-inflammatory mediators (IL-6, IL-8, TNF-α) and anti-inflammatory factors (IDO).
• Expanded PBMCs comprised CD4+ T-cells, with a significant increase in regulatory T-cells (Tregs), which demonstrated immunosuppressive capacity.

Conclusions:

• Mesenchymal stem cells can stimulate the activation and proliferation of resting T-cells, leading to the generation of regulatory T-cells.
• These findings highlight a dual role of MSCs in immune modulation, with implications for their therapeutic application.