Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT 06510, USA.
Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4669-74. doi: 10.1073/pnas.0911465107. Epub 2010 Mar 5.
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.
骨髓单核细胞（BMCs）接种的可生物降解支架是最早用于临床的组织工程血管移植物（TEVGs）。这些 TEVGs 在体内转化为有生命的血管，内皮细胞（EC）被平滑肌细胞（SMCs）包裹；然而，其发生的过程尚不清楚。为了测试接种的 BMC 是否分化为新生血管的成熟血管细胞，我们将免疫缺陷小鼠受体植入人 BMC（hBMC）接种的支架。与人类一样，作为静脉间置移植物植入小鼠宿主的 TEVGs 在 6 个月的时间过程中逐渐转化为有生命的血管。然而，在植入后几天内，就不再检测到接种的 hBMC。相反，支架最初被小鼠单核细胞重新填充，随后被小鼠 SMC 和 EC 重新填充。接种的 BMC 分泌大量单核细胞趋化蛋白-1 并增加早期单核细胞募集。这些发现表明，TEVGs 通过血管重塑的炎症过程转化为功能性新生血管。
