Hyperglycemia Induces Bioenergetic Changes in Adipose-Derived Stromal Cells While Their Pericytic Function Is...

Area of Science:

• Biomedical Engineering
• Cell Biology
• Ophthalmology

Background:

• Diabetic retinopathy (DR) is a vision-threatening complication of diabetes, characterized by microvascular damage and abnormal blood vessel growth in the retina.
• Adipose-derived stromal cells (ASC) show therapeutic potential for DR by replacing damaged pericytes, crucial cells for retinal blood vessel stability.
• The impact of hyperglycemia (HG) on the bioenergetics and functional capacity of ASC remains largely unexplored.

Purpose of the Study:

• To investigate the effects of HG on human ASC bioenergetics, mitochondrial function, and cellular viability.
• To assess the influence of HG on the ability of ASC to support endothelial cell network formation in vitro.

Main Methods:

• Human ASC were cultured under normal glucose (5 mM) and HG (30 mM) conditions.
• Cell viability, apoptosis, reactive oxygen species (ROS) production, proliferation, mitochondrial respiration, and glucose uptake were measured.
• In vitro angiogenesis assays were performed using human umbilical vein endothelial cells (HUVECs) cultured on ASC monolayers.

Main Results:

• HG significantly increased ASC apoptosis and ROS production, while proliferation remained unaffected.
• Mitochondrial function and morphology were altered by HG, leading to decreased oxygen consumption and extracellular acidification rates.
• ASC exhibited reduced glucose uptake under HG conditions.
• Despite metabolic challenges, ASC continued to promote HUVEC vascular-like network formation under HG conditions.

Conclusions:

• Hyperglycemia negatively impacts ASC bioenergetics and induces cellular stress, evidenced by increased apoptosis and ROS.
• ASC retain their capacity to support angiogenesis in vitro even when exposed to high glucose levels, suggesting potential therapeutic resilience.
• Further research is needed to fully elucidate the long-term effects of HG on ASC function and their therapeutic efficacy in DR treatment.