Image-based crosstalk analysis of cell–cell interactions during sprouting angiogenesis using blood-vessel-on-a-chip

Stem Cell Research & Therapy

Research

Jun-ichi Kawabe¹  Koharu Alicia Senda²  Takanori Sano³  Yukiko T. Matsunaga³  Yukinori Ikeda³  Shizuka Nakano³  Mizuho Yamato³  Hedele Zeng³  Tadaaki Nakajima⁴ 

[1] Department of Biochemistry, Asahikawa Medical University, 2-1-1 Midorigaoka-higashi, 078-8510, Asahikawa, Hokkaido, Japan;Hiroo Gakuen Junior and Senior High School, 5-1-14 Minami Azabu, Minato-ku, 106-0047, Tokyo, Japan;Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, 153-8505, Tokyo, Japan;Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, 153-8505, Tokyo, Japan;Department of Science, Yokohama City University, 22-2 Seto, Kanazawa-ku, 236-0027, Yokohama, Kanagawa, Japan;

关键词: Microphysiological system;    Mesenchymal stem cell;    Therapeutic angiogenesis;    Mechanosensing;   

DOI  :  10.1186/s13287-022-03223-1

 received in 2022-07-19, accepted in 2022-12-15,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundSprouting angiogenesis is an important mechanism for morphogenetic phenomena, including organ development, wound healing, and tissue regeneration. In regenerative medicine, therapeutic angiogenesis is a clinical solution for recovery from ischemic diseases. Mesenchymal stem cells (MSCs) have been clinically used given their pro-angiogenic effects. MSCs are reported to promote angiogenesis by differentiating into pericytes or other vascular cells or through cell–cell communication using multiple protein–protein interactions. However, how MSCs physically contact and move around ECs to keep the sprouting angiogenesis active remains unknown.MethodsWe proposed a novel framework of EC–MSC crosstalk analysis using human umbilical vein endothelial cells (HUVECs) and MSCs obtained from mice subcutaneous adipose tissue on a 3D in vitro model, microvessel-on-a-chip, which allows cell-to-tissue level study. The microvessels were fabricated and cultured for 10 days in a collagen matrix where MSCs were embedded.ResultsImmunofluorescence imaging using a confocal laser microscope showed that MSCs smoothed the surface of the microvessel and elongated the angiogenic sprouts by binding to the microvessel’s specific microstructures. Additionally, three-dimensional modeling of HUVEC–MSC intersections revealed that MSCs were selectively located around protrusions or roots of angiogenic sprouts, whose surface curvature was excessively low or high, respectively.ConclusionsThe combination of our microvessel-on-a-chip system for 3D co-culture and image-based crosstalk analysis demonstrated that MSCs are selectively localized to concave–convex surfaces on scaffold structures and that they are responsible for the activation and stabilization of capillary vessels.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

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