Signaling pathways activated and regulated by stem cell-derived exosome therapy

Area of Science:

• Regenerative Medicine
• Cell Biology
• Molecular Signaling

Background:

• Stem cell-derived exosomes present a cell-free therapeutic alternative, avoiding immunogenicity, tumorigenicity, and ethical concerns.
• Exosomes demonstrate therapeutic potential across diverse diseases, with flexible administration routes including systemic and local delivery.
• The therapeutic efficacy of exosomes is underpinned by their ability to activate and modulate critical cellular signaling pathways.

Purpose of the Study:

• To provide a comprehensive, pathway-oriented review of stem cell-derived exosome therapy, distinct from reviews focusing on upstream or downstream aspects.
• To meticulously analyze recent literature (past five years) on exosome-mediated signaling pathway regulation in disease management.
• To bridge the understanding between specific signaling pathways and surgical applications for future preclinical and clinical trial design.

Main Methods:

• Systematic literature review focusing on stem cell-derived exosomes and their impact on cellular signaling pathways.
• Analysis of research published within the last five years, emphasizing disease-specific and pathway-oriented findings.
• Identification and categorization of major and minor signaling pathways modulated by exosomes in various surgical specialties.

Main Results:

• Stem cell-derived exosomes regulate major signaling pathways including PTEN/PI3K/Akt/mTOR, NF-κB, TGF-β, HIF-1α, Wnt, MAPK, JAK-STAT, Hippo, and Notch.
• These pathways are modulated by exosomes in the context of diseases relevant to orthopedic, neurosurgery, cardiothoracic, plastic, and general surgery.
• Exosomes demonstrate versatility in influencing both major and minor signaling cascades for therapeutic purposes.

Conclusions:

• Stem cell-derived exosomes offer a promising cell-free therapeutic strategy by modulating critical signaling pathways.
• This review establishes a disease-specific, pathway-oriented framework for understanding exosome therapy in surgical contexts.
• Future research should leverage this understanding to design targeted preclinical studies and clinical trials for exosome-based therapeutics.