Breuer S, Fogelstrand P, Lindskog H, Osterberg K, Luebke T, Brunkwall J, Mattsson E
Department of Vascular and Endovascular Surgery, University Clinic of Cologne, Cologne, Germany -
J Cardiovasc Surg (Torino). 2014 Apr;55(2):235-46. Epub 2013 Feb 1.
Atherosclerosis with its cardiovascular events including cardiac and peripheral ischemia represents the main cause of death in the developed countries. Although interventional treatments like percutaneous transluminal angioplasty or stents are increasingly applied for the treatment of peripheral arterial disease, they are not always technically applicable or durable and bypass surgery is needed. Compared to synthetic grafts, vein grafts show a better patency especially when used for the lower leg as well as a lower risk for infection compared to synthetic grafts. Still the long-term patency rates are unsatisfactory due to accelerated intimal hyperplasia, a thickening of the vessel wall. The aim of this study was to elucidate, if the implantation of embryonic stem cells into vein grafts can reduce the development of intimal hyperplasia in a mouse in vivo model.
In this study we implanted LacZ-tagged (ROSA26) murine embryonic stem cells into decellularized vein grafts. Control groups were: 1) untreated veins; 2) decellularized veins; 3) decellularized veins with gel and plastic film; and 4) decellularized veins with smooth muscle cells in gel surrounded by plastic film. Six weeks after insertion into the carotid artery of mice, the grafts were excised and analyzed immunohistochemically, morphologically, and by x-gal staining and compared to the control groups. The Mann-Whitney U test was used to compare groups. Statistical significance was indicated by a value of P<0.05.
Decellularized veins with implanted stem cells showed significantly less intimal thickening compared to all control groups (intimal hyperplasia vs. luminal circumference mean±SD 7.3±3.5 µm, median 8 µm). The control groups: 1) untreated veins (60.3±25.5 µm, median 58.5 µm); 2) decellularized veins (53.9±22.4 µm, median 48.4 µm); 3) decellularized veins with gel and plastic film (70.6±22.4 µm, median 72.6 µm); and 4) decellularized veins with smooth muscle cells in gel surrounded by plastic film (73.5±18.1 µm, median 73.6 µm) all showed the same high degree of intimal hyperplasia.
This study demonstrates that embryonic stem cells have a therapeutic competence to favourably modulate intimal hyperplasia in vivo.
动脉粥样硬化及其心血管事件，包括心脏和外周缺血，是发达国家主要的死亡原因。尽管诸如经皮腔内血管成形术或支架等介入治疗越来越多地应用于外周动脉疾病的治疗，但它们在技术上并非总是适用或持久，因此需要进行搭桥手术。与合成移植物相比，静脉移植物具有更好的通畅性，特别是用于小腿时，并且与合成移植物相比感染风险更低。然而，由于内膜增生加速（血管壁增厚），长期通畅率仍不尽人意。本研究的目的是阐明将胚胎干细胞植入静脉移植物是否能在小鼠体内模型中减少内膜增生的发生。
在本研究中，我们将LacZ标记（ROSA26）的小鼠胚胎干细胞植入去细胞静脉移植物中。对照组为：1）未处理的静脉；2）去细胞静脉；3）带有凝胶和塑料薄膜的去细胞静脉；4）凝胶中含有平滑肌细胞且被塑料薄膜包围的去细胞静脉。将移植物植入小鼠颈动脉六周后，将其切除并进行免疫组织化学、形态学分析以及X-gal染色，并与对照组进行比较。采用Mann-Whitney U检验比较各组。P值<0.05表示具有统计学意义。
与所有对照组相比，植入干细胞的去细胞静脉内膜增厚明显较少（内膜增生与管腔周长平均值±标准差为7.3±3.5 µm，中位数为8 µm）。对照组：1）未处理的静脉（60.3±25.5 µm，中位数为58.5 µm）；2）去细胞静脉（53.9±22.4 µm，中位数为48.4 µm）；3）带有凝胶和塑料薄膜的去细胞静脉（70.6±22.4 µm，中位数为72.6 µm）；4）凝胶中含有平滑肌细胞且被塑料薄膜包围的去细胞静脉（73.5±18.1 µm，中位数为73.6 µm）均显示出相同程度的高度内膜增生。
本研究表明胚胎干细胞具有在体内有利地调节内膜增生的治疗能力。
