Serum-Mediated Oxidative Stress from Systemic Sclerosis Patients Affects Mesenchymal Stem Cell Function.

Area of Science:

• Cell Biology
• Immunology
• Regenerative Medicine

Background:

• Mesenchymal stromal cells (MSCs) are crucial for tissue repair and immune modulation.
• Systemic sclerosis (SSc) is associated with altered MSC properties, impacting potential cell-based therapies.
• Allogeneic MSCs from healthy donors are considered for SSc treatment, but their behavior in the SSc environment is unknown.

Purpose of the Study:

• To investigate the impact of the SSc serum oxidative environment on human bone marrow-derived MSC properties.
• To assess MSC proliferation, apoptosis, senescence, and functional capacities after exposure to SSc patient serum (PS).

Main Methods:

• Human bone marrow-derived MSCs were cultured with control serum (SAB) or SSc patient serum (PS).
• Cultures were supplemented with oxidative agents (HOCl or H2O2) to mimic SSc serum conditions.
• Evaluated MSCs for proliferation, apoptosis, senescence, reactive oxygen species (ROS) production, nitric oxide (NO) production, trilineage differentiation potential, and immunosuppressive function.

Main Results:

• MSCs cultured with PS showed increased senescence at day 6 and apoptosis at day 10, but retained proliferative potential in the first 3 days.
• Exposure to PS enhanced MSC antioxidant capacity, including increased SOD2 gene expression.
• Osteoblastic/adipogenic differentiation potential of MSCs increased, while immunosuppressive function was slightly reduced.

Conclusions:

• MSCs can adapt to the oxidative environment present in SSc patient serum.
• Despite some functional alterations, MSCs maintain key properties and may exert therapeutic effects in SSc.
• Further preclinical studies are warranted to confirm the therapeutic efficacy of MSCs in the SSc context.