Casein-enhanced uptake and disease-modifying bioactivity of ingested extracellular vesicles

Area of Science:

• Regenerative Medicine
• Cell Biology
• Biotechnology

Background:

• Extracellular vesicles (EVs) derived from cardiac stromal cells show therapeutic potential for muscular dystrophy.
• Parenteral administration of these EVs improves dystrophic muscle function.
• Oral delivery of EVs for therapeutic purposes has not been previously investigated.

Purpose of the Study:

• To investigate the feasibility and efficacy of oral delivery for cardiac stromal cell-derived EVs.
• To determine if casein, a milk protein, can enhance the oral absorption and bioactivity of ingested EVs.
• To evaluate the therapeutic effects of orally administered, casein-formulated EVs on muscular dystrophy.

Main Methods:

• Cardiac stromal cell-derived EVs were formulated with casein.
• EVs were administered orally to mdx mice, an animal model for muscular dystrophy.
• Changes in gene expression in blood cells and muscle function were assessed.

Main Results:

• Ingested EVs formulated with casein were absorbed and demonstrated bioactivity in vivo.
• Oral EV administration altered gene expression in blood cells.
• Muscle function was enhanced in mdx mice treated with orally delivered, casein-formulated EVs.
• Casein formulation significantly improved EV uptake and therapeutic efficacy.

Conclusions:

• Oral administration of EVs is a viable route for delivering therapeutic EVs.
• Casein enhances the uptake and bioactivity of orally ingested cardiac EVs.
• Casein-formulated EVs offer a promising, non-invasive therapeutic strategy for muscular dystrophy and potentially other conditions.