Type I collagen, fibrin and PuraMatrix matrices provide permissive environments for human endothelial and mesenchymal progenitor cells to form neovascular networks.

Type I collagen, fibrin and PuraMatrix matrices provide permissive environments for human endothelial and mesenchymal progenitor cells to form neovascular networks.
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DOI:
10.1002/term.389
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发表时间:
2011-04
影响因子:
3.3
通讯作者:
Bischoff, Joyce
Bischoff, Joyce
中科院分区:
工程技术3区
文献类型:
--
作者:
Allen, Patrick;Melero-Martin, Juan;Bischoff, Joyce

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组织工程领域寻求创造代谢要求高的功能性组织,这将需要能够在各种细胞外基质(ECM)环境中快速形成的血管网络。我们测试了人内皮祖细胞(EPCs)和间充质祖细胞(MPCs)在I型胶原蛋白、纤维蛋白和工程化肽水凝胶(PuraMatrix)中是否能在免疫缺陷小鼠体内7天形成微血管网络。这些结果与之前发表的基于Matrigel ECM的结果进行了比较。三种类型的ECM均在7天内形成灌注血管。5、6 mg/mL和10 mg/mL纤维蛋白的胶原蛋白支持血管形成30-60支血管/mm2,而PuraMatrix使血管形成160支血管/mm2,显著高于胶原蛋白或纤维蛋白。血管由内皮祖细胞组成,管腔表面有血管周围细胞。单独注射EPCs在胶原和PuraMatrix中形成了低密度的血管,而单独注射MPCs在所有测试的ecm中形成了稀疏的血管网络。使用流变仪来确定支持血管化的ecm是否具有与Matrigel相似或不同的整体物理性质。胶原蛋白和纤维蛋白是支持广泛血管形成的最坚硬的基质,其储存模量在385-510 Pa之间,而80 Pa的Matrigel和5 Pa的PuraMatrix则更加柔顺。因此,EPCs和MPCs能够在具有不同物理特性的环境中形成血管,尽管在更适应的ecm中血管密度更大。我们认为,EPC/ mpc介导的血管化是一种通用的技术,可以促进工程器官的发展。
The field of tissue engineering seeks to create metabolically demanding, functional tissues, which will require blood vessel networks capable of forming rapidly in a variety of extracellular matrix (ECM) environments. We tested whether human endothelial progenitor cells (EPCs) and mesenchymal progenitor cells (MPCs) could form microvascular networks in type I collagen, fibrin, and an engineered peptide hydrogel, PuraMatrix, in 7 days in vivo in immune-deficient mice. These results are compared to those previously published, based on the Matrigel ECM. Perfused blood vessels formed in all three types of ECM within 7 days. Collagen at 5 and 6 mg/mL and 10 mg/mL fibrin supported vessel formation at 30–60 vessels/mm2, and PuraMatrix enabled vessel formation to 160 vessels/mm2, significantly greater than collagen or fibrin. Vessels were composed of EPCs with perivascular cells on their abluminal surfaces. EPCs injected alone formed a low density of blood vessels in collagen and PuraMatrix, while MPCs injected alone resulted in sparse vessel networks in all ECMs tested. A rheometer was used to determine whether the ECMs which supported vascularization had bulk physical properties similar or distinct from Matrigel. Collagen and fibrin were the stiffest matrices to support extensive vascularization, with storage moduli from 385–510 Pa, while Matrigel, at 80 Pa, and PuraMatrix, at 5 Pa, were far more compliant. Thus, EPCs and MPCs were capable of vasculogenesis in environments having disparate physical properties, although vascular density was greater in more compliant ECMs. We propose that EPC/MPC-mediated vascularization is a versatile technology which may enable development of engineered organs.
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