Local delivery of basic fibroblast growth factor increases both angiogenesis and engraftment of hepatocytes in tissue-engineered polymer devices
Local delivery of basic fibroblast growth factor increases both angiogenesis and engraftment of hepatocytes in tissue-engineered polymer devices
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DOI：
10.1097/00007890-200205270-00011
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发表时间：
2002-05-27
期刊：
影响因子：
6.2
通讯作者：
Vacanti, JP
中科院分区：
文献类型：
--
作者：
Lee, H;Cusick, RA;Vacanti, JP
背景资料。我们研究了生物可降解聚合物上的异位肝细胞移植作为终末期肝病的潜在治疗方法。主要的问题是移植细胞的植入不足，部分原因是血管形成不足。通过局部输送血管生成因子来增加血管生成，可能会增加血管生成和肝细胞植入。我们研究了局部注射碱性成纤维细胞生长因子(BFGF)对组织工程肝组织中血管生成和肝细胞植入的影响。用生理盐水、硫糖铝和氢化物的混合物(对照组)或碱性成纤维细胞生长因子、硫糖铝和氢化物的混合物(碱性成纤维细胞生长因子组)进行涂层。用双抗体夹心法检测聚合物对碱性成纤维细胞生长因子的释放。从Lewis大鼠分离肝细胞，接种于对照组(n=9)或碱性成纤维细胞生长因子(n=11)聚合物上，种植于同基因动物的小肠系膜内。2周后取材，分析肝细胞植入情况。比较对照组(n=6)和碱性成纤维细胞生长因子(n=5)组的微血管密度。每一种聚合物中掺入的碱性成纤维细胞生长因子的含量为23.3万微克。体外培养72小时，bFGF释放率达99%以上。植入2周后，碱性成纤维细胞生长因子组微血管密度(c/hpf)显著高于对照组(30.5c/hpf，P
Background. We investigated heterotopic hepatocyte transplantation on biodegradable polymers as a potential treatment for end-stage liver disease. The primary problem has been insufficient engraftment of transplanted cells partly because of insufficient vascularization. Increasing vascularization through locally delivered angiogenic factors may increase angiogenesis and hepatocyte engraftment.Methods. We studied the effect of local delivery of basic fibroblast growth factor (bFGF) on angiogenesis and hepatocyte engraftment within tissue-engineered liver constructs. Poly-L-lactic acid discs were fabricated and coated with either a mixture of saline, sucralfate, and Hydron (control group) or bFGF, sucralfate, and Hydron (bFGF group). bFGF release from polymers in vitro was tested using an ELISA. Hepatocytes were isolated from Lewis rats, seeded on control (n=9) or bFGF (n=11) polymers, and implanted into the small bowel mesentery of syngeneic animals. Specimens were harvested after 2 weeks and analyzed for hepatocyte engraftment. Microvascular density was compared between control (n=6) and bFGF groups (n=5).Results. Three hundred twenty-three thousandths of a microgram of bFGF were incorporated per polymer. Greater than 99% of the bFGF was released into solution by 72 hr in vitro. Two weeks after implantation, microvascular density, as measured by capillaries per high-powered field (c/hpf), was significantly greater in the bFGF group (43.8 c/hpf), compared with the control group (30.5 c/hpf, P