Dual-Reporter Gene-Based Multimodal Imaging for Tracking Mesenchymal Stem Cells in Diabetic Skin Wound Repair

Area of Science:

• Regenerative Medicine
• Biomaterials Science
• Stem Cell Biology

Background:

• Diabetic foot ulcers (DFU) exhibit poor healing and limited therapeutic options.
• Mesenchymal stem cell (MSC) transplantation shows promise for DFU repair.
• Low MSC survival and lack of in vivo tracking hinder MSC efficacy in DFU.

Purpose of the Study:

• To develop a multimodal stem cell-scaffold system for enhanced DFU repair.
• To enable real-time, non-invasive tracking of transplanted MSCs in vivo.
• To improve MSC survival and therapeutic efficacy in the DFU microenvironment.

Main Methods:

• Engineered MSCs to co-express near-infrared fluorescent protein (iRFP) and ferritin heavy chain (FTH1).
• Integrated iRFP/FTH1-MSCs with a fibrin glue (FG) scaffold for a unified platform.
• Utilized iRFP for fluorescence imaging and FTH1 for MRI-based localization for multimodal cell tracking.

Main Results:

• Transplanted cells persisted in the wound for approximately seven days in a diabetic mouse model.
• The iRFP/FTH1-MSCs/FG system significantly accelerated wound closure, promoting angiogenesis and hair follicle regeneration.
• Therapy enhanced fibroblast migration, collagen synthesis, and M2 macrophage polarization, activating the PI3K-AKT-VEGF pathway for improved tissue regeneration.

Conclusions:

• The multimodal stem cell-scaffold system effectively integrates cell tracking with stem cell therapy for skin wound repair.
• This approach addresses the critical need for visualizing stem cells within the wound microenvironment.
• Provides a valuable foundation for optimizing regenerative strategies for diabetic skin wounds.