Targeting and antioxidant surface-engineered mesenchymal stromal cells for enhanced erectile dysfunction therapy

Area of Science:

• Regenerative Medicine
• Biomaterials Science
• Urology

Background:

• Erectile dysfunction (ED) significantly impacts quality of life and fertility.
• Mesenchymal stromal cell (MSC) therapy shows promise for ED but faces challenges like poor cell retention and survival.
• Factors such as rapid blood flow, oxidative stress, and inflammation in the corpus cavernosum limit MSC efficacy.

Purpose of the Study:

• To develop an effective surface engineering strategy for MSCs to enhance their retention, survival, and therapeutic outcomes in ED.
• To investigate the role of polydopamine nanoparticles and anti-Vascular Cell Adhesion Molecule 1 (VCAM-1) antibodies in improving MSC performance.
• To assess the efficacy of engineered MSCs in preclinical models of ED.

Main Methods:

• Surface engineering of MSCs using polydopamine nanoparticles conjugated to antibodies against VCAM-1.
• In vitro evaluation of engineered MSCs for survival under oxidative stress and targeting capabilities.
• In vivo assessment of engineered MSCs in rat and beagle models of ED, evaluating cell retention, inflammation, tissue pathology, and erectile function.

Main Results:

• Engineered MSCs demonstrated enhanced retention and survival in the corpus cavernosum.
• Polydopamine and anti-VCAM-1 conjugation improved MSC targeting to inflamed endothelium and mitigated reactive oxygen species (ROS) damage.
• In vivo studies showed reduced local ROS and inflammation, reversal of tissue damage, and restoration of erectile function in ED models.
• The engineering process was rapid, mild, and maintained cell viability.

Conclusions:

• Surface engineering of MSCs with polydopamine nanoparticles and VCAM-1 antibodies is a facile and translatable strategy to overcome limitations in MSC-based ED therapy.
• This approach significantly enhances MSC retention, survival, and therapeutic efficacy in preclinical ED models.
• The engineered MSCs offer a promising therapeutic avenue for improving erectile function and patient quality of life.