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Cell Squeezing as a Robust, Microfluidic Intracellular Delivery Platform
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Engineering cells with intracellular agent-loaded microparticles to control cell phenotype.

James A Ankrum1, Oscar R Miranda1, Kelvin S Ng1

  • 11] Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2] Harvard-MIT Division of Health Sciences and Technology, Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.

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Summary

Researchers engineered cells with internal depots to control their function after transplantation. This breakthrough in cell therapy offers sustained control over cell behavior for days to weeks, enhancing regenerative medicine potential.

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Area of Science:

  • Biotechnology
  • Regenerative Medicine
  • Cell Therapy

Background:

  • Cell therapies hold great promise for tissue repair, tumor destruction, and regeneration.
  • A major hurdle in cell therapy is controlling transplanted cell fate and function.
  • Existing methods lack sustained control over cellular behavior post-transplantation.

Purpose of the Study:

  • To develop a platform for sustained control of cell phenotype in vitro and after transplantation.
  • To engineer cells with intracellular depots releasing phenotype-altering agents.
  • To provide a protocol for generating and utilizing these engineered cell systems.

Main Methods:

  • Engineering cells with intracellular depots of phenotype-altering agents (e.g., dexamethasone, rhodamine, iron oxide).
  • Utilizing a single-emulsion evaporation technique to create ~1-μm agent-doped poly(lactic-co-glycolic) acid (PLGA) microparticles.
  • Developing protocols for particle preparation, cell engineering, internalization confirmation, and troubleshooting.

Main Results:

  • Demonstrated sustained release of agents from intracellular depots for days to weeks.
  • Showcased control over cell secretome, viability, proliferation, and differentiation.
  • Established efficient cell engineering and confirmed particle internalization.

Conclusions:

  • The developed platform enables precise, long-term control of cell phenotype and function.
  • This approach significantly advances the potential of cell therapies for various medical applications.
  • The provided protocol facilitates the generation and application of these engineered cells.