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Development of a transendothelial shuttle by macrophage modification
Johan Georg Visser1, Carine Smith1
1Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.
Journal of Tissue Engineering and Regenerative Medicine
|December 2, 2017
Summary
Macrophages were engineered to deliver stem cells for tissue regeneration. This novel method prevents cargo digestion while maintaining cell migration and engulfment capabilities, offering a new approach for targeted therapies.
Area of Science:
- Regenerative Medicine
- Cell Biology
- Immunology
Background:
- Limited stem cell availability hinders tissue regeneration in chronic diseases like myodystrophy and cardiovascular disease.
- Autologous macrophages offer a potential solution as delivery vehicles for stem cells and therapeutics.
- M1 phenotype macrophages possess transendothelial migration capabilities, crucial for infiltrating damaged tissues.
Purpose of the Study:
- To engineer M1 macrophages as stem cell delivery vehicles by inducing phagosome maturation arrest.
- To maintain macrophage phagocytic engulfment and transendothelial migration capabilities post-modification.
- To assess the efficacy of a wortmannin-concanamycin A-chloroquine cocktail in preventing phagosome digestion.
Main Methods:
- Primary human M1 macrophages were treated with a specific drug cocktail to induce phagosome maturation arrest.
- Modified macrophages were loaded with fluorescent latex beads (simulating stem cells).
- Phagocytic capacity, migratory response to MCP-1, and phagosome acidification were evaluated using Transwell assays and pHrodo®.
Main Results:
- The drug cocktail successfully prevented phagosome acidification, significantly limiting cargo digestion (1.23% vs. 7.52% in controls).
- Macrophage phagocytic engulfment capacity remained largely unaffected (68.67% vs. 61.19%).
- Transendothelial migration capacity was preserved, with no significant difference observed between treated and control groups (70.14% vs. 72.86%).
Conclusions:
- M1 macrophages can be effectively modified into transendothelial delivery vehicles for stem cells or drugs.
- The engineered macrophages retain essential functions, including phagocytosis and migration.
- This approach presents a novel, non-invasive strategy for targeted delivery in regenerative medicine and chronic disease treatment.
