DNA-Programmed Stem Cell Niches via Orthogonal Extracellular Vesicle-Cell Communications

Area of Science:

• Biotechnology
• Molecular Biology
• Cell Biology

Background:

• Extracellular vesicles (EVs) are crucial for intercellular communication and have potential in biomedical applications.
• Current methods for engineering EV-cell interactions, especially across species, are limited.
• A facile and generalizable approach for controlled interspecies EV-cell communication is needed.

Purpose of the Study:

• To develop a DNA-based system for engineering orthogonal interspecies EV-cell communication without genetic or covalent modifications.
• To demonstrate specific and efficient cellular internalization of EVs across species and kingdoms.
• To explore the application of this system in maintaining stem cell properties without feeder cells.

Main Methods:

• Utilized cholesterol-modified DNA strands and tetrahedral DNA frameworks as artificial ligands and receptors.
• Employed complementary DNA sequences for specific binding via Watson-Crick base pairing.
• Demonstrated EV internalization by human cells from mouse, watermelon, and E. coli, and functional delivery to monkey FGSCs.

Main Results:

• Successfully engineered specific and efficient EV internalization across diverse species (human, mouse, watermelon, E. coli) using DNA programming.
• Established orthogonal EV-cell communication circuits in complex environments.
• Showcased the delivery of bioactive EV contents to monkey female germline stem cells (FGSCs), supporting their self-renewal and stemness maintenance.

Conclusions:

• The DNA-programmed system provides a universal platform for customizing intercellular material and signal exchange across species and kingdoms.
• This approach overcomes limitations in current EV engineering, enabling novel biomedical applications.
• The technology facilitates feeder-cell-free maintenance of FGSCs, with implications for regenerative medicine.