Department of Bioengineering, University of California, Los Angeles, California 90095, USA.
Tissue Eng Part A. 2011 Jul;17(13-14):1819-30. doi: 10.1089/ten.TEA.2010.0708. Epub 2011 May 6.
Vascularization is a major challenge in tissue engineering. The purpose of this study is to expedite the formation of blood vessels in porous polycaprolactone (PCL) scaffolds by the delivery of endothelial progenitor cells (EPCs). To establish a pro-angiogenic and pro-vasculogenic microenvironment, we employed EPCs seeded in PCL scaffold with surface-immobilized heparin and vascular endothelial growth factor (VEGF). EPCs seeded on scaffolds with VEGF exhibited phosphorylation of the receptor. After 7 days of subcutaneous implantation in immunodeficient mice, heparin-immobilized PCL scaffolds with VEGF induced significantly high density of blood vessel formation. The anastomosis of EPC-derived vessels with the host circulatory system was evident by the presence of murine erythrocytes in the lumen of human-CD31 positive vessels. A more uniform distribution of blood vessels was achieved within 2-mm thick scaffolds by seeding an optimal density of EPCs. The seeding of a higher density of EPC resulted in an increase in apoptosis and a concomitant decline in blood vessel formation at the scaffold's inner core. When co-seeded with other cells, the EPCs maintained the ability to accelerate vessel formation. The excessive expansion of EPCs in vitro was associated with a decline in their in vivo vasculogenic potential. EPCs accelerated the vascularization of heparin-immobilized PCL scaffolds in the presence of VEGF.
血管生成是组织工程中的一个主要挑战。本研究的目的是通过内皮祖细胞（EPCs）的输送来加速多孔聚己内酯（PCL）支架中血管的形成。为了建立促血管生成和促血管生成的微环境，我们将 EPC 接种在表面固定肝素和血管内皮生长因子（VEGF）的 PCL 支架上。在支架上接种 VEGF 的 EPC 表现出受体的磷酸化。在免疫缺陷小鼠皮下植入 7 天后，肝素固定的 VEGF 诱导的 PCL 支架可显著诱导高密度的血管形成。在人-CD31 阳性血管的管腔中存在鼠红细胞，证明 EPC 衍生的血管与宿主循环系统的吻合。通过在最佳密度的 EPC 上接种，可在 2 毫米厚的支架内实现更均匀的血管分布。EPC 接种密度的增加导致细胞凋亡增加，同时支架内部核心的血管形成减少。当与其他细胞共接种时，EPC 仍能保持加速血管形成的能力。EPC 在体外过度扩增与体内血管生成潜能下降有关。在 VEGF 存在的情况下，EPC 加速了肝素固定的 PCL 支架的血管化。
