Roxana Paola Gómez Ruiz

Mexico

SCOPING REVIEW ON EXOSOMES AS A POTENTIAL NOVEL THERAPEUTIC OPTIONS IN DIABETIC WOUNDS

Roxana P. Gómez-Ruiz 1, Miguel A. Gómez-Sámano 1

Department: Endocrinology and Metabolism Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico

Abstract

Background

One of the most prevalent complications of diabetes mellitus is diabetic foot ulcers, characterized by chronic non-healing wounds, impaired vascularization, excessive inflammation and decreased fibroblast activity. These factors contribute to delayed wound healing and significant morbidity.
Recently, adipose-derived stem cell exosomes (ADSC-EXOs) have been suggested as a promising effective treatment option for wound healing and tissue regeneration. Exosomes are small extracellular vesicles (30-150 nm) that facilitate intercellular communication by delivering bioactive molecules, including cytokines, growth factors, and microRNAs. Hyperglycemic conditions greatly impact endothelial progenitor cell functions, including growth, migration, and angiogenesis, mainly due to oxidative stress, mitochondrial dysfunction, and inflammatory responses, which impair the healing process. This review aims to explore the potential of ADSC-EXOs in accelerating wound healing, particularly in diabetic conditions.

Methods

The literature search was conducted using the terms “exosomes AND diabetic AND wound AND healing”, across the several databases: PubMed, Web of Science, and Google Scholar. The search methodology adhered to the PRISMA guidelines.

Results

ADSC-EXOs can modulate cellular processes critical for wound repair. For instance, overexpression of Nrf2 in ADSC-EXOs has been shown to promote cell proliferation and angiogenesis, two key processes necessary for efficient wound healing. In addition, studies indicate that hyperglycemia can lead to increased PAQR3 expression and decreased of Twist1, disrupting endothelial progenitor cell function and exacerbating wound healing delays. On the other hand, ADSC-EXOs can activate the ERK/MAPK pathway, enhancing the collagen I/collagen III ratio, TGF-?3/TGF-?1, and MMP3/TIMP. This modulation promotes extracellular matrix remodeling and reduces scar formation. Additionally, ADSC-EXOs can be internalized by fibroblasts, stimulating cell migration, proliferation, and collagen synthesis in a dose-dependent manner. The expression genes like N-cadherin, cyclin-1, PCNA, and collagen I/III increases, contributing to enhanced tissue regeneration.

Conclusions

ADSC-EXOs show great promise in improving wound healing in diabetic conditions, by modulating inflammation, promoting angiogenesis, and support extracellular matrix remodeling, offering a potential cell-free therapeutic approach for tissue regeneration.