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  4. Boosting extracellular vesicle secretion

Boosting extracellular vesicle secretion

Biotechnology Advances, 2022 · DOI: https://doi.org/10.1016/j.biotechadv.2022.107983 · Published: May 16, 2022

PharmacologyGeneticsBiomedical

Simple Explanation

Extracellular vesicles (EVs), including exosomes, are nanoscale lipid bilayer membrane capsules secreted by cells. They contain proteins and genetic materials for local or systemic cell communications. Multiple EV-based therapies have been developed in recent years as a novel and alternative strategy to cell therapies to treat various medical conditions, such as cancer, cardiovascular, neurological and orthopedic diseases. This review discusses novel methods to stimulate EV production and consider their strengths and limitations. We explore physical methods, such as mechanical loading, geometry, acoustic and electrical stimulation, as well as several non-physical protocols, including molecular interference, environmental factors and external inducers.

Study Duration
Not specified
Participants
Not specified
Evidence Level
Review paper

Key Findings

  • 1
    Mechanical loading, such as shear stress or cyclic tension, can significantly increase EV secretion, potentially by over 100-fold.
  • 2
    Switching from traditional 2D cell culture to 3D geometries can enhance EV yield, with some studies showing a 3- to 10-fold increase in secretion.
  • 3
    Various molecular interventions, like inhibiting glycolysis or manipulating endolysosomal trafficking, can boost exosome production, offering alternative strategies for enhancing EV yield.

Research Summary

Extracellular vesicles (EVs), particularly exosomes, hold promise for treating various diseases and promoting tissue regeneration. However, current production methods suffer from low yield and scalability issues. This review explores diverse strategies to enhance EV yield through physical, biological, and chemical means, highlighting methods that can significantly increase production. The discussed methods, including mechanical stimulation, geometric changes, molecular interference, and environmental factors, offer potential pathways for improving EV production for clinical translation.

Practical Implications

Improved Scalability

Implementing strategies like mechanical loading and 3D culture can enable large-scale EV production, making EV-based therapies more accessible.

Enhanced Therapeutic Potential

Stimulating cells to produce EVs with altered cargos via molecular interference can improve their therapeutic functionality.

Optimized Production Protocols

Combining various stimulation methods, such as environmental factors with physical stimulation, may further enhance EV secretion value.

Study Limitations

  • 1
    The downstream mechanism of EV secretion elevation has not been thoroughly investigated for each of the stimulants.
  • 2
    Effective concentration of certain molecules works in specific cell lines may not work in other cell lines.
  • 3
    Whether acidity is efficient in therapeutically relevant cell types, such as MSCs, has yet to be investigated.

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