In Vitro Multitissue Interface Model Supports Rapid Vasculogenesis and Mechanistic Study of Vascularization across Tissue Compartments.
In Vitro Multitissue Interface Model Supports Rapid Vasculogenesis and Mechanistic Study of Vascularization across Tissue Compartments.
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DOI：
10.1021/acsami.6b01194
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发表时间：
2016-08-31
影响因子：
9.5
通讯作者：
Voytik-Harbin, Sherry L.
中科院分区：
文献类型：
--
作者：
Buno, Kevin P.;Chen, Xuemei;Weibel, Justin A.;Thiede, Stephanie N.;Garimella, Suresh V.;Yoder, Mervin C.;Voytik-Harbin, Sherry L.
关键词：
组织工程师面临的一个重大挑战是设计和开发复杂的多组织系统，包括血管组织-组织界面。虽然传统的体外模型侧重于血管生成(血管新生)或血管生成(从现有血管或内皮细胞单层萌发的血管)，但成功的治疗血管形成策略可能依赖于这两个过程的协调整合。为了应对这一挑战，我们开发了一种新的体外多组织界面模型，在该模型中，包裹了人内皮细胞克隆形成细胞(ECFC)的组织球包埋在周围的组织微环境中。这种高度可重复性的方法利用双亲表面(具有不同的超疏水和亲水区域的纳米结构表面)来(I)支持具有用户指定的基质组成和物理特性以及细胞类型和密度的组织隔间，以及(Ii)引入边界条件，以防止常规三维单分散培养中常规观察到的细胞介导的组织收缩。这一多组织界面模型被用来检验细胞-细胞外基质(ECM)和细胞-细胞相互作用的独立控制将影响组织球体内以及跨组织-组织界面的血管形成的假设。我们发现，含有5×106个ECFCs/mL的高细胞密度组织球具有快速而强劲的血管生成能力，仅在3天内就形成了高度互联的、稳定的(由IV型胶原沉积所示)血管网络。在周围组织中添加脂肪来源的基质细胞(ASCs)进一步促进球体内的血管生成以及跨越组织-组织边界的血管生成延长，这两种效果都依赖于ASC的密度。总体而言，结果表明，就旁分泌和机械物理信号而言，ECFC密度和ECFC-ASC串扰是特定组织间和跨组织界面血管形成的关键决定因素。这一新的体外多组织界面模型及其产生的相关机制见解为研究和临床应用的多组织血管化策略的设计和优化提供了指导原则。
A significant challenge facing tissue engineers is the design and development of complex multitissue systems, including vascularized tissue–tissue interfaces. While conventional in vitro models focus on either vasculogenesis (de novo formation of blood vessels) or angiogenesis (vessels sprouting from existing vessels or endothelial monolayers), successful therapeutic vascularization strategies will likely rely on coordinated integration of both processes. To address this challenge, we developed a novel in vitro multitissue interface model in which human endothelial colony forming cell (ECFC)-encapsulated tissue spheres are embedded within a surrounding tissue microenvironment. This highly reproducible approach exploits biphilic surfaces (nanostructured surfaces with distinct superhydrophobic and hydrophilic regions) to (i) support tissue compartments with user-specified matrix composition and physical properties as well as cell type and density and (ii) introduce boundary conditions that prevent the cell-mediated tissue contraction routinely observed with conventional three-dimensional monodispersion cultures. This multitissue interface model was applied to test the hypothesis that independent control of cell–extracellular matrix (ECM) and cell–cell interactions would affect vascularization within the tissue sphere as well as across the tissue–tissue interface. We found that high-cell-density tissue spheres containing 5 × 106 ECFCs/mL exhibit rapid and robust vasculogenesis, forming highly interconnected, stable (as indicated by type IV collagen deposition) vessel networks within only 3 days. Addition of adipose-derived stromal cells (ASCs) in the surrounding tissue further enhanced vasculogenesis within the sphere as well as angiogenic vessel elongation across the tissue–tissue boundary, with both effects being dependent on the ASC density. Overall, results show that the ECFC density and ECFC–ASC crosstalk, in terms of paracrine and mechanophysical signaling, are critical determinants of vascularization within a given tissue compartment and across tissue interfaces. This new in vitro multitissue interface model and the associated mechanistic insights it yields provide guiding principles for the design and optimization of multitissue vascularization strategies for research and clinical applications.
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影响因子：
3.3
作者：
Holnthoner, Wolfgang;Hohenegger, Karin;Redl, Heinz
通讯作者：
Redl, Heinz
影响因子：
4.8
作者：
Heiss, Maximilian;Hellstrom, Mats;Korff, Thomas
通讯作者：
Korff, Thomas
DOI：
10.1007/b138509
发表时间：
2006-01-01
期刊：
TISSUE ENGINEERING I: SCAFFOLD SYSTEMS FOR TISSUE ENGINEERING
影响因子：
--
作者：
Lu, Helen H.;Jiang, Jie
通讯作者：
Jiang, Jie
影响因子：
4.6
作者：
Chen X;Patel RS;Weibel JA;Garimella SV
通讯作者：
Garimella SV
影响因子：
3.3
作者：
Allen, Patrick;Melero-Martin, Juan;Bischoff, Joyce
通讯作者：
Bischoff, Joyce