Effects of Extracellular Matrix Density and Mesenchymal Stem Cells on Neovascularization In Vivo
Effects of Extracellular Matrix Density and Mesenchymal Stem Cells on Neovascularization In Vivo
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DOI：
10.1089/ten.tea.2010.0275
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发表时间：
2011-04-01
影响因子：
4.1
通讯作者：
Putnam, Andrew J.
中科院分区：
文献类型：
--
作者：
Kniazeva, Ekaterina;Kachgal, Suraj;Putnam, Andrew J.
异常的血管生成是常见的多种疾病，其中也发生组织机械性质的改变。对血管生成和组织结构特性的相互依赖性的基本理解可能会促进治疗策略的发展。我们以前建立了细胞外基质密度的增加抑制体外三维组织中的毛细血管形态发生，并且加入人间充质干细胞（MSC）部分挽救了健康的血管生成表型。本研究的目的是调查这些影响是否可以在体内重现。将人脐静脉内皮细胞、MSC或两者的混合物悬浮在5、10和15 mg/mL浓度的纤维蛋白凝胶前体溶液中，并皮下注射到SCID小鼠中。通过量化血管数量、灌注、厚度、成熟度和血管周围胶原沉积，在3、7和21天回收的组织结构中评估新血管形成。数据表明，细胞外基质密度的变化抑制体内毛细血管形态发生的方式与体外观察到的一致。在所有组织浓度下，人脐静脉内皮细胞和MSC两者的递送比单独递送任一细胞类型产生更稳健和成熟的血管。
Aberrant angiogenesis is common to a variety of diseases in which alterations in tissue mechanical properties also occur. A fundamental understanding of the interdependence of angiogenesis and tissue structural properties may enhance the development of therapeutic strategies. We previously established that increasing extracellular matrix density inhibits capillary morphogenesis in three-dimensional tissues in vitro, and that addition of human mesenchymal stem cells (MSCs) partially rescues a healthy angiogenic phenotype. This study's goal was to investigate if these effects can be recapitulated in vivo. Human umbilical vein endothelial cells, MSCs, or a mixture of both was suspended in fibrin gel precursor solutions of 5, 10, and 15 mg/mL concentrations and injected subcutaneously into SCID mice. Neovascularization was assessed in tissue constructs retrieved at 3, 7, and 21 days by quantifying vessel numbers, perfusion, thickness, maturity, and perivascular collagen deposition. The data show that changing extracellular matrix density inhibits capillary morphogenesis in vivo in a manner consistent with that observed in vitro. Delivery of both human umbilical vein endothelial cells and MSCs produced more robust and mature vessels than delivery of either cell type alone in all tissue concentrations.