Surface-Engineered Mitochondria with Targeting Potential for Endothelial Repair.

Area of Science:

• Biomedical Engineering
• Cell Biology
• Vascular Biology

Background:

• Mitochondrial dysfunction is a key factor in endothelial injury associated with vascular diseases.
• Current mitochondria transplantation methods lack specificity, efficient uptake, and long-term retention.
• Developing targeted endothelial repair strategies is crucial for treating vascular conditions.

Purpose of the Study:

• To engineer mitochondria for enhanced delivery to the vascular endothelium.
• To improve the specificity, uptake, and retention of transplanted mitochondria.
• To establish a foundation for novel cell-free therapeutics for vascular repair.

Main Methods:

• Isolated mitochondria from induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs).
• Surface-functionalized mitochondria using a DSPE-PEG coating platform with VCAM-1 and collagen-binding peptides for targeted delivery.
• Assessed mitochondrial characteristics, cellular uptake, retention, and function in human diabetic aortic endothelial cells (DAECs).

Main Results:

• Surface functionalization significantly enhanced mitochondrial uptake in DAECs compared to uncoated mitochondria.
• Engineered mitochondria exhibited increased cytoplasmic retention and colocalization with the host mitochondrial network.
• Recipient cells showed improved mitochondrial membrane potential and sustained oxygen consumption, indicating restored bioenergetic function.

Conclusions:

• Demonstrated a proof-of-concept for surface-engineered mitochondria to improve transplantation to damaged endothelium.
• Surface engineering enhances cellular uptake and bioenergetic restoration in recipient endothelial cells.
• These findings support the development of adaptable, cell-free therapeutics for vascular disease treatment.