Engineered ADSC-Exo-bFGF significantly accelerates skin wound healing and collagen deposition via PI3K/AKT activation.
Background
Effective wound healing is a complex process crucial for tissue repair, yet chronic wounds remain a significant clinical challenge. Current treatments often fall short in promoting comprehensive regeneration and mitigating inflammation. Adipose-derived stem cell (ADSC)-derived exosomes show promise due to their regenerative properties, and basic fibroblast growth factor (bFGF) is a known potent stimulator of tissue repair. However, the specific therapeutic efficacy and underlying molecular mechanisms of bFGF-modified ADSC exosomes in cutaneous wound healing have been largely unelucidated, representing a key gap this study addresses.
Study Design
Researchers constructed a bFGF-glycosylphosphatidylinositol (GPI)-anchored exosome system (ADSC-Exo-bFGF) by transfecting ADSCs with a eukaryotic expression plasmid carrying the bFGF-GPI fusion gene. Secreted exosomes were isolated and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. In vivo, the therapeutic efficacy was assessed in a skin wound model, with histological evaluation via Hematoxylin and Eosin (H&E) staining and Masson's trichrome staining. Inflammatory cytokines were quantified by ELISA. In vitro, Cell Counting Kit-8 (CCK-8) assay evaluated human skin fibroblast (HSF) viability, and scratch assay determined migration. Protein levels of bFGF and PI3K/AKT pathway components were assessed by western blot.
Results
Isolated ADSC-Exo-bFGF exhibited positive expression of characteristic exosomal surface markers and abundant bFGF protein. In vivo results confirmed that ADSC-Exo-bFGF treatment significantly accelerated skin wound healing compared to control groups. This engineered exosome system also reduced inflammatory infiltration and enhanced collagen deposition, demonstrating better therapeutic effects than unmodified ADSC-derived exosomes. In vitro experiments further verified that ADSC-Exo-bFGF promoted the proliferation and migration of human skin fibroblasts (HSFs) and suppressed inflammatory factors in cell supernatants. The study also found that these beneficial effects correlated with the activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. This suggests a direct molecular mechanism for the observed regenerative and anti-inflammatory actions.
ADSC-Exo-bFGF treatment significantly accelerated skin wound healing, reduced inflammatory infiltration, and enhanced collagen deposition in vivo, outperforming unmodified ADSC-derived exosomes.
Key Findings
- ADSC-Exo-bFGF exosomes were successfully constructed and characterized, expressing abundant bFGF protein.
- ADSC-Exo-bFGF treatment significantly accelerated skin wound healing in vivo compared to controls.
- ADSC-Exo-bFGF reduced inflammatory infiltration and enhanced collagen deposition in wound tissues.
- Engineered ADSC-Exo-bFGF showed better therapeutic effects than unmodified ADSC-derived exosomes.
- ADSC-Exo-bFGF promoted proliferation and migration of human skin fibroblasts (HSFs) in vitro.
Why It Matters
This research introduces a novel, enhanced exosome-based strategy for accelerating skin wound healing, potentially offering a superior alternative to current therapies. By engineering ADSCs to secrete bFGF-anchored exosomes, the study provides a proof-of-concept for targeted delivery of growth factors, which could lead to more efficient and potent regenerative treatments. The findings suggest that modifying exosomes with specific growth factors like bFGF could be a powerful approach for chronic or difficult-to-heal wounds. While preclinical, this work lays the groundwork for developing advanced exosome therapies that leverage specific signaling pathways like PI3K/AKT to optimize tissue repair and reduce inflammation, moving closer to clinically translatable protocols for complex wound management.
adsc-exo-bfgf
wound-healing
exosomes
bfgf
pi3k-akt
inflammation