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Michael E D West1, Elana J B Sefton1, Michael V Sefton1,2

  • 11 Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.

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Allogeneic macrophages enhance engineered tissue vascular stability in vivo. Mesenchymal stromal cells influence macrophage behavior, aiding the development of larger, clinically relevant tissues with integrated vasculature.

Keywords:
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Area of Science:

  • Tissue engineering
  • Immunology
  • Vascular biology

Background:

  • Engineered tissues require robust vascularization for survival and function.
  • Achieving stable, host-integrated vasculature in engineered tissues remains a significant challenge.
  • The role of immune cells, like macrophages, in modulating vascular development is complex.

Purpose of the Study:

  • To investigate the effect of allogeneic macrophages on the stability of newly formed vasculature in engineered tissues in vivo.
  • To develop and validate a method for analyzing macrophage phenotype within vascularized explants.
  • To assess the influence of mesenchymal stromal cells (MSC) on macrophage phenotype in this context.

Main Methods:

  • Implantation of modular engineered tissues containing allogeneic macrophages into a host.
  • Histological and immunophenotypic analysis of explanted tissues to assess vascularization and macrophage characteristics.
  • Co-culture experiments to evaluate the interaction between macrophages and mesenchymal stromal cells (MSC).

Main Results:

  • Allogeneic macrophage implantation significantly enhanced the stability of engineered tissue vasculature.
  • A detailed method for macrophage phenotyping in vascularized explants was established.
  • Mesenchymal stromal cells (MSC) modulated the phenotype of implanted macrophages, influencing the vascularization process.

Conclusions:

  • Allogeneic macrophages represent a viable strategy for improving engineered tissue vascular stability.
  • The developed analytical methods allow for detailed characterization of immune cell-tissue interactions.
  • Understanding and manipulating macrophage phenotype, potentially with MSC, is crucial for advancing vascularized tissue engineering.