Mimicking the inflammatory cell adhesion cascade by nucleic acid aptamer programmed cell-cell interactions.

Area of Science:

• Biomaterials Engineering
• Cell Therapy
• Immunology

Background:

• Therapeutic cells often fail to target diseased tissues after infusion, a major hurdle in cell therapy.
• Nature utilizes cell adhesion mechanisms for inflammatory cell delivery, a process not inherent in culture-expanded cells.

Purpose of the Study:

• To develop simple methods for programming cell-cell interactions for targeted delivery.
• To engineer mesenchymal stem cells (MSCs) for enhanced tissue targeting and to study cell-cell interactions.

Main Methods:

• Engineered MSCs by attaching P- or L-selectin binding nucleic acid aptamers using a chemistry approach.
• Assessed cell adhesion under static and dynamic flow conditions (≤2 dyn/cm²).
• Utilized control groups including scrambled-DNA modified MSCs.

Main Results:

• Engineered MSCs demonstrated >10-fold increased adhesion to selectin surfaces compared to controls under static conditions.
• Engineered MSCs were successfully captured from a flow stream by selectin surfaces or selectin-expressing cells.
• Demonstrated recapitulation of key inflammatory cell adhesion cascade interactions with a single artificial ligand.

Conclusions:

• A simple chemistry approach using aptamers can engineer specific cell-cell interactions.
• Aptamer-engineered MSCs show enhanced targeting capabilities for potential therapeutic applications.
• This versatile method can be broadly applied to target cells to diseased tissues and understand cell interaction biology.