Macrophages Play a Key Role in Angiogenesis and Adipogenesis in a Mouse Tissue Engineering Model

Abstract

We have previously described a mouse adipose tissue engineering model using a silicon chamber enclosing the superficial epigastric pedicle in a Matrigel based environment. We have shown that when Zymosan, a sterile inflammatory agent, is added to the chamber, angiogenesis and adipogenesis are significantly improved. As Zymosan interacts with toll-like receptors on macrophages, the role of macrophages in new tissue development in the tissue engineering chamber was assessed. Morphological and histological results showed that macrophages were presenting in high numbers at 2 weeks but had decreased significantly by 4 and 6 weeks in the chamber. Numerous immature new blood vessels had formed by 2 weeks, becoming more mature at 4 and 6 weeks. Immature adipocytes were visualized at 4 weeks and mature cells, at 6 weeks. To investigate the functional role of macrophages in the tissue engineering process, we knocked out the local macrophage population by inserting Clodronate liposomes in this chamber. This study shows for the first time that when macrophages are depleted, there is minimal new vascular and adipose tissue development. We propose a new theory for tissue engineering in which macrophages play a central role in both neovascularisation and adipogenesis.

Delivered adipose‐derived stromal cells improve host‐derived adipose tissue formation in composite constructs in vivo

“…With regard to ASCs acting as modulators of the host response, they are well acknowledged for producing a wide panel of cytokines with an angiogenic, hematopoietic, and proinflammatory profile, which may act as key inductive molecules and exert effects on cell recruitment and subsequent tissue development . In this context, early macrophage infiltration is discussed to be intrinsic for adipose tissue formation as shown by Debels et al Macrophages are known for their ability to degrade and remodel the extracellular matrix, thereby enabling tissue development, to promote angiogenesis and even to differentiate into adipocyte‐like cells; however, the putative role of these recruited host cells in the generation of adipose tissue remains to be further elucidated.…”

Do adipose tissue macrophages promote insulin resistance or adipose tissue remodelling in humans?

“…In vitro, administration of anti-VEGF antibodies inhibited angiogenesis and the formation of adipogenic and angiogenic cell clusters, suggesting that this is essential for differentiation of adipocytes. Debels et al [105] examined a murine tissue engineering model following addition of zymogen as an inflammatory agent, to a Matrigel matrix. In this context, macrophages were observed at 2 weeks, along with immature new blood vessels.…”

Transferring the exudate in the tissue engineering chamber as a trigger to incubate large amount adipose tissue in remote area

“…It has been confirmed in many researches that TEC model has the ability to induce large volume of adipogenesis (Debels et al, ; Dolderer et al, ; Findlay et al, ). Here, we use the unique FDM to testify our hypothesis.…”