Merckx Greet, Tay Hanna, Lo Monaco Melissa, van Zandvoort Marc, De Spiegelaere Ward, Lambrichts Ivo, Bronckaers Annelies
Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium.
Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Tissue Eng Part B Rev. 2020 Dec;26(6):519-539. doi: 10.1089/ten.TEB.2020.0048. Epub 2020 May 1.
Tissue engineering aims to structurally and functionally regenerate damaged tissues, which requires the formation of new blood vessels that supply oxygen and nutrients by the process of angiogenesis. Stem cells are a promising tool in regenerative medicine due to their combined differentiation and paracrine angiogenic capacities. The study of their proangiogenic properties and associated potential for tissue regeneration requires complex models comprising all steps of the angiogenic process. The highly vascularized extraembryonic chorioallantoic membrane (CAM) of fertilized chicken eggs offers a simple, easy accessible, and cheap angiogenic screening tool compared to other animal models. Although the CAM assay was initially primarily performed for evaluation of tumor growth and metastasis, stem cell studies using this model are increasing. In this review, a detailed summary of angiogenic observations of different mesenchymal, cardiac, and endothelial stem cell types and derivatives in the CAM model is presented. Moreover, we focus on the variation in experimental setup, including the benefits and limitations of and protocols, diverse biological and synthetic scaffolds, imaging techniques, and outcome measures of neovascularization. Finally, advantages and disadvantages of the CAM assay as a model for angiogenesis in tissue engineering in comparison with alternative animal models are described. Impact statement The chorioallantoic membrane (CAM) assay is an easy and cheap screening tool for the angiogenic properties of stem cells and their associated potential in the tissue engineering field. This review offers an overview of all published angiogenic studies of stem cells using this model, with emphasis on the variation in used experimental timeline, culture protocol ( vs. ), stem cell type (derivatives), scaffolds, and outcome measures of vascularization. The purpose of this overview is to aid tissue engineering researchers to determine the ideal CAM experimental setup based on their specific study goals.
组织工程旨在从结构和功能上再生受损组织,这需要通过血管生成过程形成新的血管来供应氧气和营养物质。干细胞因其兼具分化能力和旁分泌血管生成能力,成为再生医学中一种很有前景的工具。对其促血管生成特性及相关组织再生潜力的研究需要包含血管生成过程所有步骤的复杂模型。与其他动物模型相比,受精鸡蛋高度血管化的胚外尿囊膜(CAM)提供了一种简单、易于获取且廉价的血管生成筛选工具。尽管CAM试验最初主要用于评估肿瘤生长和转移,但使用该模型的干细胞研究正在增加。在这篇综述中,我们详细总结了CAM模型中不同间充质干细胞、心脏干细胞和内皮干细胞类型及其衍生物的血管生成观察结果。此外,我们重点关注实验设置的差异,包括不同方案的优缺点、多种生物和合成支架、成像技术以及新生血管形成的结果指标。最后,描述了与其他替代动物模型相比,CAM试验作为组织工程中血管生成模型的优缺点。影响声明尿囊膜(CAM)试验是一种用于评估干细胞血管生成特性及其在组织工程领域相关潜力的简单且廉价的筛选工具。本综述概述了所有已发表的使用该模型的干细胞血管生成研究,重点关注所用实验时间线、培养方案(与 )、干细胞类型(衍生物)、支架以及血管化结果指标的差异。本综述的目的是帮助组织工程研究人员根据其特定研究目标确定理想的CAM实验设置。