Are plant exosomes (extracellular vesicles) effective and safe for use in medical treatments, particularly for skin health and regeneration?

Plant Exosomes in Medical Treatments: Current Evidence and Limitations

Plant exosomes (extracellular vesicles) are not currently recommended for routine clinical use in medical treatments due to significant methodological limitations, lack of standardization, and insufficient clinical evidence regarding their safety and efficacy. 1

Current Status of Plant Exosome Research

Plant-derived exosome-like nanovesicles (PELNs) have generated interest as potential therapeutic delivery systems due to several theoretical advantages:

• Similar physical and chemical properties to mammalian exosomes 2
• Potential economic advantages as an affordable source of production 3
• Ability to carry therapeutic compounds including nucleic acids, proteins, and lipids 4
• Possible applications in targeted drug delivery, gene therapy, and tissue regeneration 4

However, several critical limitations prevent their clinical implementation:

Major Limitations

• Lack of standardized protocols: No universally agreed protocol exists for isolating pure populations of exosomes 5, 1
• Isolation challenges: Contamination with proteins and lipoproteins remains problematic 5
• Characterization issues: Difficulty distinguishing exosomes from non-vesicular particles 5
• Limited stability data: Exosomes appear stable at -80°C, but this is impractical for pharmaceutical products 6
• Unknown pharmacokinetics: Limited information on bio-distribution and circulation time 5
• Rapid clearance: Unmodified EVs are rapidly cleared by the liver and spleen 5
• Safety concerns: High concentrations of EVs administered intravenously have caused rapid asphyxiation in animal models 5

Potential Applications Being Investigated

Despite these limitations, research continues to explore potential applications:

1. Drug delivery systems:

   • Plant exosomes may be combined with nanoparticle-based systems to increase stability and targeting 4
   • May enable controlled release and targeted distribution to specific tissues 4

2. Gene therapy:

   • Plant exosomes can be modified to carry nucleic acids like plasmid DNA, siRNA, or miRNA 4
   • Potential for therapeutic gene expression regulation 2

3. Regenerative medicine:

   • Possible applications in tissue regeneration 4
   • Potential for skin health and regeneration applications 7

Current Recommendations for Clinical Practice

The European Society of Cardiology Working Group provides several recommendations regarding exosome research that apply to plant exosomes 5, 1:

• Avoid precipitation methods for exosome isolation
• Use exosome-free conditions for tissue culture
• Confirm presence of at least 3 marker proteins for characterization
• Assess levels of contaminating proteins
• Determine size distribution using two orthogonal techniques
• Include complete experimental details and report all negative data

Future Requirements for Clinical Translation

Before plant exosomes can enter clinical practice, several developments are necessary:

• Development of GMP-quality isolation methods and validation procedures 5
• Standardized protocols for production and characterization 7
• Better understanding of their mechanism of action 7
• Comprehensive safety and toxicity studies 5
• Detailed pharmacokinetic studies 5
• Clinical trials demonstrating efficacy 7

Conclusion

While plant exosomes show theoretical promise for medical applications including skin health and regeneration, the current evidence does not support their clinical use. Companies must invest in more research to develop standardized and reliable procedures for their isolation, characterization, and application before they can be approved for clinical practice 7.