Williams S K, Rose D G, Jarrell B E
Department of Surgery, University of Arizona Health Sciences Center, Tucson 85724.
J Biomed Mater Res. 1994 Feb;28(2):203-12. doi: 10.1002/jbm.820280210.
Small diameter (< 6 mm) synthetic vascular grafts fail at a clinically unacceptable rate due in large part to their inherent thrombogenicity. The development of a new cellular lining on synthetic vascular grafts would most likely improve the patency rates observed for these grafts in small diameter positions. We have evaluated the use of endothelial cell transplantation to accelerate the formation of a cell lining using microvascular endothelial cells derived from canine falciform ligament fat. This source of fat is histologically similar to human liposuction fat and was isolated using a collagenase digestion technique identical to methods used for human liposuction fat microvessel endothelial cell isolation. The isolated fat endothelial cells were sodded onto 4 mm ePTFE grafts using pressure to force the cells onto the luminal surface. This pressure sodding method permitted cell deposition in less then 3 min. Sodded and control (non-cell-treated) grafts were implanted as interpositional paired grafts using end-to-end anastomoses in the carotid arteries of mixed breed dogs. Each dog therefore received a sodded graft on one side and a control graft on the contralateral side. After 12 weeks of implantation all control grafts were occluded while 86% of the cell-sodded grafts remained patent. Statistical evaluation of the data revealed a significant improvement in patency of cell sodded grafts (McNemar's chi 2 P = .02). Morphological evaluation of grafts explanted at 5, 12, 26, and 52 weeks following implantation revealed the presence of a cell lining on sodded grafts which remained stable for a period of at least one year. This new cell lining exhibited morphologic characteristics of a nonthrombogenic endothelial cell lining. The development of this new intima, evaluated 5 weeks-1 year after implantation, was not associated with a progressive intimal hyperplasia. From these data we conclude that microvessel endothelial cells derived from canine falciform ligament fat can be rapidly isolated using an operating room compatible method. Cell deposition on synthetic grafts is subsequently accelerated using a pressure sodding technique. A cellular lining forms on the inner surface and is associated with a statistically significant improvement in the function of sodded grafts in a canine carotid artery model.
小直径（<6毫米）的合成血管移植物由于其固有的血栓形成性，在临床上失败率高得令人无法接受。在合成血管移植物上形成新的细胞内衬很可能会提高这些移植物在小直径位置的通畅率。我们评估了使用内皮细胞移植来加速细胞内衬形成的方法，所用的微血管内皮细胞来源于犬镰状韧带脂肪。这种脂肪来源在组织学上与人类抽脂脂肪相似，并且使用与人类抽脂脂肪微血管内皮细胞分离方法相同的胶原酶消化技术进行分离。将分离出的脂肪内皮细胞通过施压使其附着在4毫米的ePTFE移植物上，从而迫使细胞附着在管腔表面。这种压力附着方法可在不到3分钟内实现细胞沉积。将附着细胞的移植物和对照（未进行细胞处理）移植物作为间置配对移植物，通过端对端吻合术植入杂种犬的颈动脉。因此，每只狗一侧植入附着细胞的移植物，另一侧植入对照移植物。植入12周后，所有对照移植物均闭塞，而86%的附着细胞移植物仍保持通畅。对数据的统计评估显示，附着细胞移植物的通畅率有显著提高（McNemar卡方检验P = 0 .02）。对植入后5周、12周、26周和52周取出的移植物进行形态学评估，发现附着细胞的移植物上存在细胞内衬，且这种内衬至少在一年内保持稳定。这种新的细胞内衬表现出非血栓形成性内皮细胞内衬的形态学特征。植入后5周 - 1年评估的这种新内膜的形成与内膜增生进展无关。从这些数据中我们得出结论，使用手术室适用的方法可以快速分离出源自犬镰状韧带脂肪的微血管内皮细胞。随后使用压力附着技术加速细胞在合成移植物上的沉积。内表面形成细胞内衬，并且在犬颈动脉模型中，附着细胞的移植物功能在统计学上有显著改善。
