Vascular endothelial growth factor-releasing scaffolds enhance vascularization and engraftment of hepatocytes transplanted on liver lobes
Vascular endothelial growth factor-releasing scaffolds enhance vascularization and engraftment of hepatocytes transplanted on liver lobes
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DOI：
10.1089/ten.2005.11.715
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发表时间：
2005-05-01
影响因子：
--
通讯作者：
Cohen, S
中科院分区：
文献类型：
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作者：
Kedem, A;Perets, A;Cohen, S
多孔支架（HT）内的肝细胞移植正在探索作为终末期肝病和酶缺乏症的治疗策略。这种方法的主要问题之一是移植细胞的活力有限，因为支架部位的血管化太慢或不足。现在，我们通过持续输送血管内皮生长因子（VEGF）来增强细胞移植前的支架血管化，并通过检查肝叶作为将供体肝细胞移植到靠近宿主肝脏的平台来解决这个问题。通过分析植入后第 3、7 和 14 天收获的植入物中的微血管密度和组织向内生长，评估大鼠肝叶上未接种的 VEGF 释放支架的血管化动力学。释放 VEGF 的支架中的毛细血管密度始终高于未补充 VEGF 的对照支架；第 14 天，毛细血管数量为 220 +/- 33 与 139 +/- 23 毛细血管/mm(2) (p < 0.05)。此外，在VEGF释放支架中，35%的新形成的毛细血管直径大于16μm，而在对照支架中，只有10%超过这个尺寸。 VEGF 对组织向支架内生长没有影响。 Lewis 大鼠肝叶预血管化 1 周后，对植入的 VEGF 释放支架或对照支架进行 HT。在第 1、3、7 和 12 天收获 50 个植入物，并评估活肝细胞的面积。增强的血管化改善了肝细胞植入； HT后12天，VEGF释放支架中的完整肝细胞面积(136,910μm(2)/横截面)比对照组高4.6。这项研究表明，持续局部输送 VEGF 可诱导植入肝叶的多孔支架的血管化，并改善肝细胞植入。
Hepatocyte transplantation within porous scaffolds ( HT) is being explored as a treatment strategy for end-stage liver diseases and enzyme deficiencies. One of the main issues in this approach is the limited viability of transplanted cells because vascularization of the scaffold site is either too slow or insufficient. We now address this by enhancing scaffold vascularization before cell transplantation via sustained delivery of vascular endothelial growth factor (VEGF), and by examining the liver lobes as a platform for transplanting donor hepatocytes in close proximity to the host liver. The vascularization kinetics of unseeded VEGF-releasing scaffolds on rat liver lobes were evaluated by analyzing the microvascular density and tissue ingrowth in implants harvested on days 3, 7, and 14 postimplantation. Capillary density was greater at all times in VEGF-releasing scaffolds than in the control scaffold without VEGF supplementation; on day 14, it was 220 +/- 33 versus 139 +/- 23 capillaries/mm(2) (p < 0.05). Furthermore, 35% of the newly formed capillaries in VEGF-releasing scaffolds were larger than 16 mu m in diameter, whereas in control scaffolds only 10% exceeded this size. VEGF had no effect on tissue ingrowth into the scaffolds. HT onto the implanted VEGF-releasing or control scaffolds was performed after 1 week of prevascularization on the liver lobe in Lewis rats. Fifty implants were harvested on days 1, 3, 7, and 12 and the area of viable hepatocytes was evaluated. The enhanced vascularization improved hepatocyte engraftment; 12 days after HT, the intact hepatocyte area (136,910 mu m(2)/cross-section) in VEGF- releasing scaffolds was 4.6 higher than in the control group. This study shows that sustained local delivery of VEGF induced vascularization of porous scaffolds implanted on liver lobes and improved hepatocyte engraftment.