Host Environment Determines Vascular Patterning and Cardiomyocyte Engraftment
Brady EL, Prado O, Johansson F, Mitchell SN, Martinson AM, Karbassi E, Reinecke H, Murry CE, Davis J, Stevens KR. Engineered tissue vascularization and engraftment depends on host model. Sci Rep 202;13(1):1973. doi: 10.1038/s41598-022-23895-2.
Background: Developing engineered tissues that integrate with host vasculature is a key challenge in regenerative medicine. Previous studies have focused on constructing human vascular networks within engineered tissues before implantation, yet the influence of the host environment on graft vascularization and cell survival remains underexplored. Understanding how host species and implant site affect vascular integration is essential for improving the reproducibility and efficacy of engineered tissue engraftment.
Hypothesis: This study hypothesized that the host animal model and anatomic implant location critically determine vascularization and cardiomyocyte engraftment outcomes in human engineered tissues implanted in vivo.
Methods: The authors fabricated fibrin-based tissues containing patterned endothelial “cords” and cardiomyocytes, implanted them on the heart or in the abdomen of athymic nude mice and rats, and analyzed explants using histology and immunostaining. Vessel morphology was quantified from 3D confocal images using Vesselucida, with vessel diameter and geometry analyzed via Vesselucida Explorer.
Results: In mice, endothelial cords guided the formation of patterned, blood-filled vessels with larger lumens and minimal inflammation in both abdominal and epicardial sites. In contrast, rat implants showed pronounced inflammation, collagen deposition and loss of vascular patterning. Despite disrupted vessel organization, rats exhibited over threefold larger human cardiomyocyte grafts than mice.
Conclusions: Host biology strongly influences engineered tissue vascularization and engraftment, demonstrating that vascular and cardiac integration require distinct host conditions, with significant implications for translational tissue engineering.
