Use of human aortic extracellular matrix as a scaffold for construction of a patient-specific tissue engineered vascular patch
Use of human aortic extracellular matrix as a scaffold for construction of a patient-specific tissue engineered vascular patch
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使用人主动脉细胞外基质作为支架构建患者特异性组织工程血管补片
DOI：
10.1088/1748-605x/aa801b
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发表时间：
2017-12-01
影响因子：
4
通讯作者：
Li, Jun
中科院分区：
文献类型：
--
作者：
Gao, Li-Ping;Du, Ming-Jun;Li, Jun
合成材料或生物材料通常用于修复先天性心脏病中的血管畸形；然而，非自体材料存在顺应性不匹配和抗原性问题，且其表面缺乏细胞再植。在此，我们利用手术中切除的人主动脉获取的脱细胞细胞外基质（ECM）支架构建了一种组织工程血管补片（TEVP），并在其上接种了患者来源的骨髓CD34阳性（CD34 +）祖细胞。在去除细胞成分的同时，脱细胞的ECM支架保留了天然的ECM成分，具有与未脱细胞的主动脉组织相似的力学性能，并支持CD34 +祖细胞的黏附、存活和增殖。有趣的是，在体外将脱细胞的主动脉ECM支架接种21天后，CD34 +祖细胞在未添加任何生长因子的情况下分化为成熟的血管内皮细胞，这通过内皮表面标志物（CD31、血管性血友病因子（VWF）、血管内皮钙黏蛋白和细胞间黏附分子 - 2）水平的升高以及基因水平（CD31、VWF和内皮型一氧化氮合酶）的上调，同时干细胞标志物（CD133和CD34）表达的降低得以证实，从而导致脱细胞ECM支架的表面内皮化。因此，本研究中构建的针对患者个体的TEVP在血管畸形的儿科患者临床应用中具有巨大潜力。
Synthetic or biologic materials are usually used to repair vascular malformation in congenital heart defects; however, non-autologous materials show both mismatch compliance and antigenicity, as well as a lack of recellularization on its surface. Here, we constructed a tissue-engineered vascular patch (TEVP) using decellularized extracellular matrix (ECM) scaffold obtained from excised human aorta during surgery, which was seeded with patient-derived bone marrow CD34-positive (CD34+) progenitor cells. While cellular components were removed, the decellularized ECM scaffold retained native ECM composition, similar mechanical performance to undecellularized aortic tissue, and supported the adhesion, survival and proliferation of CD34+ progenitor cells. Interestingly, after in vitro seeding of decellularized aortic ECM scaffold for 21 d, CD34+ progenitor cells differentiated into mature vascular endothelial cells without addition of any growth factors, as confirmed by the increased levels of endothelial surface markers (CD31, Von Willebrand factor (VWF), VE-cadherin and ICAM-2) and upregulated gene levels (CD31, VWF and eNOS) concurrently with decreased expression of stem cell markers (CD133 and CD34), thus, resulting in surface endothelialization of decellularized ECM scaffold. Consequently, the patient-specific TEVP constructed in this study holds great potential for clinical use in pediatric patients with vascular malformation.