Bone Marrow-Derived Macrophages Enhance Vessel Stability in Modular Engineered Tissues.

IMPACT STATEMENT: This work demonstrates an effective method of enhancing the stability of a newly formed vasculature in modular engineered tissues in vivo through the counterintuitive implantation of allogeneic macrophages. Furthermore, we provide a detailed method for analyzing macrophage phenotype in vascularized explants and assess the role of added mesenchymal stromal cells (MSC) on that phenotype. Enhanced vascular stability may permit the development of increasingly large, clinically relevant tissues, fully permeated by blood vessels integrated with the host vasculature.

In vivo remodelling of vascularizing engineered tissues.

A critical aspect of creating vascularized tissues is the remodelling that occurs in vivo, driven in large part by the host response to the tissue construct. Rather than a simple inflammatory response, a beneficial tissue remodelling response results in the formation of vascularised tissue. The characteristics and dynamics of this response are slowly being elucidated, especially as they are modulated by the complex interaction between the biomaterial and cellular components of the tissue constructs and the host. This process has elements that are similar to both wound healing and tumour development, and its features are illustrated by reference to the bottom-up generation of a tissue using modular constructs. These modular constructs consist of mesenchymal stromal cells (MSC) embedded in endothelial cell (EC)-covered collagen gel rods that are a few hundred microns in size. Particular attention is paid to the role of hypoxia and macrophage recruitment, as well as the paracrine effects of the MSC and EC in this host response.