Quantitative evaluation of endothelial progenitors and cardiac valve endothelial cells:: Proliferation and differentiation on poly-glycolic acid/poly-4-hydroxybutyrate scaffold in response to vascular endothelial growth factor and transforming growth factor β1
Quantitative evaluation of endothelial progenitors and cardiac valve endothelial cells:: Proliferation and differentiation on poly-glycolic acid/poly-4-hydroxybutyrate scaffold in response to vascular endothelial growth factor and transforming growth factor β1
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DOI：
10.1089/107632703322066660
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发表时间：
2003-06-01
影响因子：
--
通讯作者：
Bischoff, J
中科院分区：
文献类型：
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作者：
Dvorin, EL;Wylie-Sears, J;Bischoff, J
由生物可吸收聚合物成分制成的三维支架目前正在测试用于各种组织的组织工程。聚乙醇酸(PGA)非织造网浸渍在1%的聚-4-羟基丁酸酯(P4HB)溶液中的复合支架被证明是适合于在绵羊体内建立组织工程三叶肺瓣膜置换术的支架[Hoerstrup，S.P.，等人，循环102(增刊.3)，III44,2000]。然而，种植在PGA/P4HB上的细胞在体外对培养液中提供的可溶性因子的反应却知之甚少。为了优化体外组织发育，在植入之前，我们开始开发定量生化分析来测量种植在PGA/P4HB上的细胞对生长和分化因素的反应。在此，我们发现种植在PGA/P4HB上的绵羊主动脉瓣内皮细胞和循环内皮祖细胞(EPC)在血管内皮生长因子的作用下增殖，在转化生长因子β(1)的作用下向间充质表型转化。从内皮细胞表型向间充质细胞表型的转分化是心脏瓣膜胚胎发育的关键步骤。我们的结果表明，从外周血中分离的瓣膜内皮细胞和内皮祖细胞可以概括PGA/P4HB的关键发育步骤。这些结果表明PGA/P4HB；为细胞的增殖、分化和组织发育提供了有利的环境。
Three-dimensional scaffolds made of bioabsorbable polymeric constituents are currently being tested for use in tissue engineering of various tissues. A composite scaffold of poly-glycolic acid (PGA) non-woven mesh dip-coated in a 1% solution of poly-4-hydroxybutyrate (P4HB) was shown to be suitable as a scaffold for creation of tissue-engineered trileaflet pulmonic valve replacements in sheep [Hoerstrup, S.P., et al, Circulation 102(Suppl. 3), III44, 2000]. However, little is known about how cells seeded on PGA/P4HB respond in vitro to soluble factors supplied in the culture medium. To optimize tissue development in vitro, before implantation, we set out to develop quantitative biochemical assays to measure how cells seeded on PGA/P4HB respond to growth and differentiation factors. Herein we show that ovine aortic valvular endothelial cells and circulating endothelial progenitor cells (EPCs) seeded onto PGA/P4HB proliferate in response to vascular endothelial growth factor and transdifferentiate to a mesenchymal phenotype in response to transforming growth factor beta(1). Transdifferentiation from an endothelial to mesenchymal phenotype is a critical step during embryonic development of cardiac valves. Our results demonstrate that valvular endothelial cells and EPCs isolated from peripheral blood can recapitulate critical developmental steps on PGA/P4HB. These results demonstrate that PGA/P4HB; provides a conducive environment for cellular proliferation, differentiation, and tissue development.