Synergistic effect of sustained delivery of basic fibroblast growth factor and bone marrow mononuclear cell transplantation on angiogenesis in mouse ischemic limbs
Synergistic effect of sustained delivery of basic fibroblast growth factor and bone marrow mononuclear cell transplantation on angiogenesis in mouse ischemic limbs
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DOI：
10.1016/j.biomaterials.2005.09.009
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发表时间：
2006-03-01
期刊：
影响因子：
14
通讯作者：
Kim, BS
中科院分区：
文献类型：
--
作者：
Jeon, O;Kang, SW;Kim, BS
对于肢体缺血的治疗，联合血管生成疗法可能优于单一血管生成疗法上级。首先，我们研究了碱性成纤维细胞生长因子（bFGF）的管理和骨髓来源的单核细胞（BMMNC）移植的血管生成的功效是否可以增强持续交付（SD）的bFGF和BMMNC移植使用的矩阵，分别在小鼠缺血肢体。接下来，我们研究了两种血管生成策略组合的血管生成功效是否优于单独使用的任何一种策略的上级。在手术诱导小鼠后肢缺血后一天，将小鼠随机分为不接受治疗、每天注射（131）bFGF、SD bFGF。使用培养基的BMMNC移植，使用纤维蛋白基质（FM）的BMMNC移植，或bFGF的SD与使用FM的BMMNC移植的组合。bFGF的SD与DI相比，微血管密度显著增加（659 ± 48/mm 2对522 ± 39/mm 2，p < 0.05）。与使用培养基的BMMNC移植相比，使用FM的BMMNC移植显著增加了微血管密度（523 +/- 103/mm（2）2对415 +/- 75/mm，p < 0.05）。重要的是，与单独的策略相比，bFGF缓释与使用FM的BMMNC移植的组合进一步增加了微血管和小动脉的密度（p < 0.05）。血管生成蛋白的SD方法和基质细胞移植分别增强bFGF和BMMNC移植治疗肢体缺血的血管生成功效。此外，与每种单独治疗相比，bFGF SD和BMMNC移植的联合治疗可协同增强小鼠缺血肢体的血管生成。(c)2005爱思唯尔有限公司保留所有权利。
Combined angiogenic therapies may be superior to single angiogenic therapy for treatment of limb ischemia. First, we investigated whether the angiogenic efficacy of basic fibroblast growth factor (bFGF) administration and bone marrow-derived mononuclear cell (BMMNC) transplantation can be enhanced by sustained delivery (SD) of bFGF and BMMNC transplantation using a matrix, respectively, in mouse ischemic limbs. Next, we investigated whether the angiogenic efficacy of combination of two angiogenic strategies is superior to either strategy alone. One day after surgical induction of mouse hindlimb ischemia, mice were randomized to receive either no treatment, daily injection (131) of bFGF, SD of bFGF.. BMMNC transplantation using culture medium, BMMNC transplantation using fibrin matrix (FM), or combination of SD of bFGF with BMMNC transplantation using FM. The SD of bFGF significantly increased the microvessel density, compared with DI of bFGF (659 +/- 48/mm 2 versus 522 +/- 39/mm(2), p < 0.05). BMMNC transplantation using FM significantly increased the microvessel density, compared with BMMNC transplantation using culture medium (523 +/- 103/mm(2) 2 versus 415 +/- 75/mm, p < 0.05). Importantly, combination of bFGF sustained release with BMMNC transplantation using FM further increased the densities of microvessels and arterioles, compared to either strategy alone (p < 0.05). The SD method of angiogenic protein and cell transplantation using matrix potentiate the angiogenic efficacy of bFGF and BMMNC transplantation, respectively, for limb ischemia. In addition, the combined therapy of SD of bFGF and BMMNC transplantation synergistically enhances angiogenesis in mouse ischemic limb, compared to each separate therapy. (c) 2005 Elsevier Ltd. All rights reserved.