Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht University, Maastricht, The Netherlands.
Tissue Eng Part A. 2012 Apr;18(7-8):828-39. doi: 10.1089/ten.TEA.2011.0284. Epub 2012 Jan 26.
Short-term thrombotic occlusion and compliance mismatch hamper clinical use of synthetic small-diameter tissue engineered vascular grafts. It is felt that preconditioning of the graft with intimal (endothelial) and medial (vascular smooth muscle) cells contributes to patency of the graft. Autologous, non-vessel-derived cells are preferred because of systemic vascular pathology and immunologic concerns. We tested in a porcine model whether cultured bone marrow-derived mononuclear cells, also referred to as mesenchymal stem cells (MSC), are a potential source of intimal or medial cells in vascular tissue engineering. We show that MSC cultured in endothelial medium do not gain an endothelial phenotype or functional characteristics, even after enrichment for CD31, culturing under flow, treatment with additional growth factors (vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2), or co-culture with microvascular endothelial cells (EC). On the other hand, we show that MSC cultured in MSC medium, but not in smooth muscle cell medium, show phenotypical and functional characteristics of vascular smooth muscle cells. We conclude that bone marrow-derived MSCs can be used as a bona fide source of medial, but not EC in small-diameter vascular tissue engineering.
短期血栓闭塞和顺应性不匹配阻碍了合成小直径组织工程血管移植物的临床应用。人们认为,用内膜(内皮)和中膜(血管平滑肌)细胞对移植物进行预处理有助于移植物的通畅。由于全身血管病理和免疫问题,首选自体、非血管来源的细胞。我们在猪模型中测试了培养的骨髓来源的单核细胞,也称为间充质干细胞(MSC),是否是血管组织工程中内膜或中膜细胞的潜在来源。我们表明,即使在 CD31 富集、在流动下培养、用额外的生长因子(血管内皮生长因子(VEGF)、成纤维细胞生长因子(FGF)-2)处理或与微血管内皮细胞(EC)共培养后,在内皮培养基中培养的 MSC 也不会获得内皮表型或功能特征。另一方面,我们表明,在 MSC 培养基中培养的 MSC,但不在平滑肌细胞培养基中培养的 MSC,表现出血管平滑肌细胞的表型和功能特征。我们得出结论,骨髓来源的 MSC 可作为小直径血管组织工程中中膜的可靠来源,但不能作为 EC 的来源。