Macrophages of diverse phenotypes drive vascularization of engineered tissues

Macrophages are key contributors to vascularization, but the mechanisms behind their actions are not understood. Here, we show that diverse macrophage phenotypes have distinct effects on endothelial cell behavior, with resulting effects on vascularization of engineered tissues. In Transwell cocultur...

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Bibliographic Details
Published in:Science advances 2020-05, Vol.6 (18), p.eaay6391-eaay6391
Main Authors: Graney, P L, Ben-Shaul, S, Landau, S, Bajpai, A, Singh, B, Eager, J, Cohen, A, Levenberg, S, Spiller, K L
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation
Endothelial Cells
Engineering
Life Sciences
Macrophages
Mice
Phenotype
SciAdv r-articles
Tissue Engineering
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Summary:Macrophages are key contributors to vascularization, but the mechanisms behind their actions are not understood. Here, we show that diverse macrophage phenotypes have distinct effects on endothelial cell behavior, with resulting effects on vascularization of engineered tissues. In Transwell coculture, proinflammatory M1 macrophages caused endothelial cells to up-regulate genes associated with sprouting angiogenesis, whereas prohealing (M2a), proremodeling (M2c), and anti-inflammatory (M2f) macrophages promoted up-regulation of genes associated with pericyte cell differentiation. In 3D tissue-engineered human blood vessel networks in vitro, short-term exposure (1 day) to M1 macrophages increased vessel formation, while long-term exposure (3 days) caused regression. When human tissue-engineered blood vessel networks were implanted into athymic mice, macrophages expressing markers of both M1 and M2 phenotypes wrapped around and bridged adjacent vessels and formed vessel-like structures themselves. Last, depletion of host macrophages inhibited remodeling of engineered vessels, infiltration of host vessels, and anastomosis with host vessels.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.aay6391