Hyaluronan Induces a Mitochondrial Functional Switch in Fast-Proliferating Human Mesenchymal Stem

Area of Science:

• Stem cell biology
• Biochemistry
• Mitochondrial function

Background:

• Hyaluronan (HA) is crucial for mesenchymal stem cell (MSC) proliferation and differentiation.
• Coated-surface hyaluronan (CHA) maintains MSCs in a slow-proliferating state by upregulating mitochondrial biogenesis.
• The metabolic effects of soluble hyaluronan (SHA) on MSCs remain largely unknown.

Purpose of the Study:

• To investigate the impact of SHA at varying concentrations (0.001 mg/ml and 5 mg/ml) on MSC mitochondrial function.
• To compare the effects of SHA with CHA and control conditions on MSCs' energetic status.
• To elucidate the metabolic pathways utilized by MSCs under different hyaluronan culture conditions.

Main Methods:

• Human placenta-derived MSCs (PDMSCs) were cultured with SHA (0.001 mg/ml and 5 mg/ml) and CHA (5.0 and 30 μg/cm²).
• Mitochondrial mass, DNA copy number, and oxygen consumption rate were measured.
• ATP content and lactate production were quantified to assess cellular energy metabolism.

Main Results:

• PDMSCs cultured with SHA (0.001 mg/ml) showed reduced mitochondrial mass, DNA copy number, and oxygen consumption compared to those cultured with CHA.
• SHA-cultured cells exhibited a 2-fold increase in ATP content and lactate production.
• This suggests a metabolic shift towards glycolysis in fast-proliferating MSCs under SHA conditions.

Conclusions:

• Both CHA and SHA treatments led to a reduction in reactive oxygen species (ROS) levels in PDMSCs.
• SHA promotes a glycolytic shift in MSCs, differing from the mitochondrial upregulation seen with CHA.
• These findings provide critical insights into how different hyaluronan application methods influence stem cell metabolism and function, relevant for cell therapies.