3.8 Article

Comparative Studies of Fibrin-Based Engineered Vascular Tissues and Notch Signaling from Progenitor Cells

期刊

ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 6, 期 5, 页码 2696-2706

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.0c00255

关键词

vascular tissues; fibrin gel; Notch signaling

资金

  1. Heart and Stroke Foundation of Canada

向作者/读者索取更多资源

The main impetus of vascular tissue engineering is clinical translation, but an equally appealing and impactful use of engineered vascular tissues is as preclinical testing platforms for studying vascular disease and developing therapeutic drugs and understanding of physiologically relevant vascular biology. Developing model engineered tissues will aid in narrowing the significant knowledge gaps in functional tissue formation, which is regulated by intricate cell signaling in a three-dimensional space. In this study, we fabricated tubular engineered vascular tissues using cross-linked fibrinogen as a scaffold and nondifferentiated embryonic rat vascular smooth muscle cell line (A10 cells) and mouse embryonic multipotent mesenchymal progenitor cell line (10T1/2 cells) as model vascular cells. Fibrin gel dimensional contraction kinetics study showed that A10 cells embedded in the gel were unable to significantly contract the tissue compared to fibrin-only gels because of their undifferentiated state. In contrast, 10T1/2 cells differentiated with TGF-beta 1 to a vascular lineage were able to contract the tubular gel significantly owing to the contractile cytoskeletal stress fibers. Because of its vital role in vascular morphogenesis, tissue specification, and maturation, Notch signaling studies in engineered vascular tissues from A10 cells demonstrated cis-inhibition, whereas 10T1/2 cells activated Notch and its downstream targets Hes-1 and the smooth muscle alpha-actin genes. Taken together, this study showed that (i) contrary to the previously accepted notion, cell-type is important to gel contractions, and (ii) in engineered vascular tissues, Notch signaling is highly context-dependent, where cis-inhibition muted signal activation in A10 vascular cells, whereas Notch was fully activated in 10T1/2 cells. These findings may provide insights to fabricate functional vascular tissues.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

3.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据