Construction of Continuous Capillary Networks Stabilized by Pericyte-like Perivascular Cells

Kyoko Yamamoto, Kohei Tanimura, Masafumi Watanabe, Hiromu Sano, Hiroyuki Uwamori, Yo Mabuchi, Yumi Matsuzaki, Seok Chung, Roger D. Kamm, Kazuo Tanishita, Ryo Sudo

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Construction of small and continuous capillary networks is a fundamental challenge for the development of three-dimensional (3D) tissue engineering. In particular, to construct mature and stable capillary networks, it is important to consider interactions between endothelial cells and pericytes. This study aimed to construct stable capillary networks covered by pericyte-like perivascular cells, which maintain the lumen of small diameter similar to that of capillary structures in vivo. Vascular sprouting, capillary extension, and stabilization were investigated using a 3D angiogenesis model containing human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) in a microfluidic device. A series of HUVEC:MSC ratios was tested; the ratio was found to be an important factor in the construction of capillary structures. We found that stable capillary networks that were covered by MSC-derived perivascular cells can be constructed at 1:1 HUVEC:MSC ratio. The constructed capillary networks had continuous lumens with <10-μm diameter, which were maintained for at least 21 days. This angiogenic process and basement membrane formation were regulated by HUVEC-MSC interactions. Construction of capillary networks is a fundamental challenge for the development of three-dimensional (3D) tissue engineering. However, it is not well understood how to construct stable capillary networks that maintain a luminal size similar to that of capillary structures in vivo (i.e., <10 μm diameter). In this study, we demonstrated the construction of stable capillary networks covered by pericyte-like perivascular cells using an in vitro 3D angiogenesis model by optimizing interactions between endothelial cells and perivascular cells. Our 3D angiogenesis model can be combined with 3D culture of epithelial cells in the context of vascularization of 3D tissue-engineered constructs.

Original languageEnglish
Pages (from-to)499-510
Number of pages12
JournalTissue Engineering - Part A
Volume25
Issue number5-6
DOIs
Publication statusPublished - 2019 Mar

Keywords

  • 3D angiogenesis model
  • mesenchymal stem cells
  • microfluidic device
  • pericytes

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Fingerprint Dive into the research topics of 'Construction of Continuous Capillary Networks Stabilized by Pericyte-like Perivascular Cells'. Together they form a unique fingerprint.

  • Cite this

    Yamamoto, K., Tanimura, K., Watanabe, M., Sano, H., Uwamori, H., Mabuchi, Y., Matsuzaki, Y., Chung, S., Kamm, R. D., Tanishita, K., & Sudo, R. (2019). Construction of Continuous Capillary Networks Stabilized by Pericyte-like Perivascular Cells. Tissue Engineering - Part A, 25(5-6), 499-510. https://doi.org/10.1089/ten.tea.2018.0186