Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling
Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling
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DOI：
10.1073/pnas.0911465107
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发表时间：
2010-03-09
影响因子：
11.1
通讯作者：
Breuer, Christopher K.
中科院分区：
文献类型：
--
作者：
Roh, Jason D.;Sawh-Martinez, Rajendra;Breuer, Christopher K.
骨髓单个核细胞（BMCs）种植的生物可降解支架是最早应用于临床的组织工程血管移植物（TEVG）。这些TEVG在体内转化为活血管，其中内皮细胞（EC）衬里被平滑肌细胞（SMC）覆盖;然而，这发生的过程尚不清楚。为了测试接种的BMC是否分化为新血管的成熟血管细胞，我们将人BMC（hBMC）接种的支架植入免疫缺陷小鼠受体。与人类一样，作为静脉间置移植物植入小鼠宿主的TEVG在6个月的时间过程中逐渐转化为活血管。然而，接种的hBMC在植入后几天内不再可检测到。相反，支架最初由小鼠单核细胞重新填充，随后由小鼠SMC和EC重新填充。接种的BMCs分泌大量的单核细胞趋化蛋白-1，并增加早期单核细胞募集。这些发现表明TEVG通过血管重塑的炎症过程转化为功能性新血管。
Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are the earliest tissue-engineered vascular grafts (TEVGs) to be used clinically. These TEVGs transform into living blood vessels in vivo, with an endothelial cell (EC) lining invested by smooth muscle cells (SMCs); however, the process by which this occurs is unclear. To test if the seeded BMCs differentiate into the mature vascular cells of the neovessel, we implanted an immunodeficient mouse recipient with human BMC (hBMC)-seeded scaffolds. As in humans, TEVGs implanted in a mouse host as venous interposition grafts gradually transformed into living blood vessels over a 6-month time course. Seeded hBMCs, however, were no longer detectable within a few days of implantation. Instead, scaffolds were initially repopulated by mouse monocytes and subsequently repopulated by mouse SMCs and ECs. Seeded BMCs secreted significant amounts of monocyte chemoattractant protein-1 and increased early monocyte recruitment. These findings suggest TEVGs transform into functional neovessels via an inflammatory process of vascular remodeling.