Heydarkhan-Hagvall Sepideh, Esguerra Maricris, Helenius Gisela, Söderberg Rigmor, Johansson Bengt R, Risberg Bo
Department of Surgery, Vascular Engineering Centre, Sahlgrenska University Hospital, Göteborg, Sweden.
Tissue Eng. 2006 Apr;12(4):831-42. doi: 10.1089/ten.2006.12.831.
Morphology and compliance of tissue-engineered blood vessels (TEBV) are dependent on the culture period and production of extracellular matrix (ECM) components in order to increase the strength of the developing tissue. The aim of the present study was to evaluate the potential of TEBVs to produce an ECM similar to native arteries and veins. Human smooth muscle cells (SMC) were seeded onto the poly(glycolic acid) (PGA) scaffold and placed in bioreactors filled with DMEM supplemented with growth factors. After 6 weeks, the vessels were harvested from the bioreactors and seeded with human endothelial cells at the lumen for another 3 days. Then, the TEBVs were harvested for RNA and protein isolation for further RT-PCR and Western blot. TEBVs had a similar macroscopic appearance to that of native vessels with no visible evidence of the original PGA. Histological and immunohistochemical analyses indicated the presence of high cell density and development of a highly organized structure of ECM. After 6 weeks of culture, there were significantly lower gene expression of SMC-specific markers, such as alpha-actin, caldesmon, and vimentin, and proteoglycans, such as biglycan, decorin, and versican, and other ECM components, such as collagen I and elastin, in TEBVs, with and without pulsatile conditions, compared to that of native arteries. Gene expression of fibronectin was significantly lower in TEBVs grown during pulsatile conditions compared to that of native arteries. No difference was observed in TEBVs grown during non-pulsatile conditions. The presence of alpha-actin, collagen I, decorin, and fibronectin at protein level was demonstrated in TEBVs with and without pulsatile conditions after 6 weeks and in native veins and arteries as well. How this deviation translates into mechanical properties remains to be explored.
组织工程血管(TEBV)的形态和顺应性取决于培养时间以及细胞外基质(ECM)成分的产生,以增强发育中组织的强度。本研究的目的是评估TEBV产生类似于天然动脉和静脉的ECM的潜力。将人平滑肌细胞(SMC)接种到聚乙醇酸(PGA)支架上,并置于装有补充了生长因子的DMEM的生物反应器中。6周后,从生物反应器中取出血管,并在内腔接种人内皮细胞,再培养3天。然后,收获TEBV以进行RNA和蛋白质分离,用于进一步的逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析。TEBV的宏观外观与天然血管相似,未发现原始PGA的明显痕迹。组织学和免疫组织化学分析表明,细胞密度高,且ECM形成了高度有序的结构。培养6周后,无论有无搏动条件,与天然动脉相比,TEBV中SMC特异性标志物(如α-肌动蛋白、钙调蛋白和波形蛋白)、蛋白聚糖(如双糖链蛋白聚糖、核心蛋白聚糖和多功能蛋白聚糖)以及其他ECM成分(如I型胶原蛋白和弹性蛋白)的基因表达均显著降低。与天然动脉相比,在搏动条件下生长的TEBV中纤连蛋白的基因表达显著降低。在非搏动条件下生长的TEBV中未观察到差异。6周后,无论有无搏动条件,TEBV以及天然静脉和动脉中均在蛋白质水平检测到α-肌动蛋白、I型胶原蛋白、核心蛋白聚糖和纤连蛋白的存在。这种偏差如何转化为力学性能仍有待探索。