Enhanced Vascularization of Modular Engineered Tissues Using Activated Macrophages

Enhancing the vascularization of modular engineered tissues is critical for the survival of implanted therapeutic cells and the development of large, in vivo tissue constructs. However, modular implants elicit strong inflammatory responses, impairing this process. Mesenchymal stromal cells (MSC) are effective promoters of construct vascularization in vivo, and their immunomodulatory effect on inflammation and macrophage activation was assessed by flow cytometric analysis of enzymatically digested tissues. MSC limited macrophage infiltration into tissues at day 3 and caused increased vessel densities at day 7, but did not affect macrophage activation. Modular tissues containing bone marrow-derived macrophages (BMDM) activated to have pro- or anti-inflammatory phenotypes did not alter the course of inflammation or enhance vessel growth, but did stabilize existing vessels. Significant vessel regression occurred by day 14 in implants lacking BMDM, activated or otherwise. No effect due to BMDM activation was seen.