1 O'Brien Institute Melbourne , Fitzroy, Australia .
Tissue Eng Part A. 2013 Dec;19(23-24):2615-25. doi: 10.1089/ten.TEA.2013.0071. Epub 2013 Aug 21.
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.
我们之前曾描述过一种使用硅室在基于 Matrigel 的环境中封闭上腹浅蒂的小鼠脂肪组织工程模型。我们已经表明，当向腔室中添加无菌炎症剂 Zymosan 时，血管生成和脂肪生成会显著改善。由于 Zymosan 与巨噬细胞上的 toll 样受体相互作用，因此评估了巨噬细胞在组织工程腔室中新组织发育中的作用。形态学和组织学结果表明，巨噬细胞在 2 周时大量存在，但在 4 周和 6 周时腔室内的数量明显减少。在 2 周时已经形成了大量不成熟的新血管，在 4 周和 6 周时变得更加成熟。在 4 周时可以观察到不成熟的脂肪细胞，而在 6 周时则可以观察到成熟的细胞。为了研究巨噬细胞在组织工程过程中的功能作用，我们通过在该腔室中插入 Clodronate 脂质体来敲除局部巨噬细胞群。这项研究首次表明，当耗尽巨噬细胞时，新血管和脂肪组织的发育很少。我们提出了一种新的组织工程理论，其中巨噬细胞在血管生成和脂肪生成中均起核心作用。
