Transport-mediated angiogenesis in 3D epithelial coculture

Ryo Sudo, Seok Chung, Ioannis K. Zervantonakis, Vernella Vickerman, Yasuko Toshimitsu, Linda G. Griffith, Roger D. Kamm

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Increasing interest has focused on capturing the complexity of tissues and organs in vitro as models of human pathophysiological processes. In particular, a need exists for a model that can investigate the interactions in three dimensions (3D) between epithelial tissues and a microvascular network since vascularization is vital for reconstructing functional tissues in vitro. Here, we implement a microfluidic platform to analyze angiogenesis in 3D cultures of rat primary hepatocytes and rat/human microvascular endothelial cells (rMVECs/hMVECs). Liver and vascular cells were cultured on each sidewall of a collagen gel scaffold between two microfluidic channels under static or flow conditions. Morphogenesis of 3D hepatocyte cultures was found to depend on diffusion and convection across the nascent tissue. Furthermore, rMVECs formed 3D capillary-like structures that extended across an intervening gel to the hepatocyte tissues in hepatocyter-MVEC coculture while they formed 2D sheet-like structures in rMVEC monoculture. In addition, diffusion of fluorescent dextran across the gel scaffold was analyzed, demonstrating that secreted proteins from the hepatocytes and MVECs can be exchanged across the gel scaffold by diffusional transport. The experimental approach described here is useful more generally for investigating microvascular networks within 3D engineered tissues with multiple cell types in vitro.

Original languageEnglish
Pages (from-to)2155-2164
Number of pages10
JournalFASEB Journal
Volume23
Issue number7
DOIs
Publication statusPublished - 2009 Jul
Externally publishedYes

Fingerprint

Coculture Techniques
Tissue
Hepatocytes
Gels
Scaffolds
Microfluidics
Microvessels
Rats
Convection
Dextrans
Morphogenesis
Endothelial cells
Blood Vessels
Cultured Cells
Collagen
Liver
Epithelium
Endothelial Cells
In Vitro Techniques
Proteins

Keywords

  • Microfluidics
  • Tissue engineering
  • Vascularization

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

Sudo, R., Chung, S., Zervantonakis, I. K., Vickerman, V., Toshimitsu, Y., Griffith, L. G., & Kamm, R. D. (2009). Transport-mediated angiogenesis in 3D epithelial coculture. FASEB Journal, 23(7), 2155-2164. https://doi.org/10.1096/fj.08-122820

Transport-mediated angiogenesis in 3D epithelial coculture. / Sudo, Ryo; Chung, Seok; Zervantonakis, Ioannis K.; Vickerman, Vernella; Toshimitsu, Yasuko; Griffith, Linda G.; Kamm, Roger D.

In: FASEB Journal, Vol. 23, No. 7, 07.2009, p. 2155-2164.

Research output: Contribution to journalArticle

Sudo, R, Chung, S, Zervantonakis, IK, Vickerman, V, Toshimitsu, Y, Griffith, LG & Kamm, RD 2009, 'Transport-mediated angiogenesis in 3D epithelial coculture', FASEB Journal, vol. 23, no. 7, pp. 2155-2164. https://doi.org/10.1096/fj.08-122820
Sudo R, Chung S, Zervantonakis IK, Vickerman V, Toshimitsu Y, Griffith LG et al. Transport-mediated angiogenesis in 3D epithelial coculture. FASEB Journal. 2009 Jul;23(7):2155-2164. https://doi.org/10.1096/fj.08-122820
Sudo, Ryo ; Chung, Seok ; Zervantonakis, Ioannis K. ; Vickerman, Vernella ; Toshimitsu, Yasuko ; Griffith, Linda G. ; Kamm, Roger D. / Transport-mediated angiogenesis in 3D epithelial coculture. In: FASEB Journal. 2009 ; Vol. 23, No. 7. pp. 2155-2164.
@article{01f67b8348444b38832d4ef1b0f1b65b,
title = "Transport-mediated angiogenesis in 3D epithelial coculture",
abstract = "Increasing interest has focused on capturing the complexity of tissues and organs in vitro as models of human pathophysiological processes. In particular, a need exists for a model that can investigate the interactions in three dimensions (3D) between epithelial tissues and a microvascular network since vascularization is vital for reconstructing functional tissues in vitro. Here, we implement a microfluidic platform to analyze angiogenesis in 3D cultures of rat primary hepatocytes and rat/human microvascular endothelial cells (rMVECs/hMVECs). Liver and vascular cells were cultured on each sidewall of a collagen gel scaffold between two microfluidic channels under static or flow conditions. Morphogenesis of 3D hepatocyte cultures was found to depend on diffusion and convection across the nascent tissue. Furthermore, rMVECs formed 3D capillary-like structures that extended across an intervening gel to the hepatocyte tissues in hepatocyter-MVEC coculture while they formed 2D sheet-like structures in rMVEC monoculture. In addition, diffusion of fluorescent dextran across the gel scaffold was analyzed, demonstrating that secreted proteins from the hepatocytes and MVECs can be exchanged across the gel scaffold by diffusional transport. The experimental approach described here is useful more generally for investigating microvascular networks within 3D engineered tissues with multiple cell types in vitro.",
keywords = "Microfluidics, Tissue engineering, Vascularization",
author = "Ryo Sudo and Seok Chung and Zervantonakis, {Ioannis K.} and Vernella Vickerman and Yasuko Toshimitsu and Griffith, {Linda G.} and Kamm, {Roger D.}",
year = "2009",
month = "7",
doi = "10.1096/fj.08-122820",
language = "English",
volume = "23",
pages = "2155--2164",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "7",

}

TY - JOUR

T1 - Transport-mediated angiogenesis in 3D epithelial coculture

AU - Sudo, Ryo

AU - Chung, Seok

AU - Zervantonakis, Ioannis K.

AU - Vickerman, Vernella

AU - Toshimitsu, Yasuko

AU - Griffith, Linda G.

AU - Kamm, Roger D.

PY - 2009/7

Y1 - 2009/7

N2 - Increasing interest has focused on capturing the complexity of tissues and organs in vitro as models of human pathophysiological processes. In particular, a need exists for a model that can investigate the interactions in three dimensions (3D) between epithelial tissues and a microvascular network since vascularization is vital for reconstructing functional tissues in vitro. Here, we implement a microfluidic platform to analyze angiogenesis in 3D cultures of rat primary hepatocytes and rat/human microvascular endothelial cells (rMVECs/hMVECs). Liver and vascular cells were cultured on each sidewall of a collagen gel scaffold between two microfluidic channels under static or flow conditions. Morphogenesis of 3D hepatocyte cultures was found to depend on diffusion and convection across the nascent tissue. Furthermore, rMVECs formed 3D capillary-like structures that extended across an intervening gel to the hepatocyte tissues in hepatocyter-MVEC coculture while they formed 2D sheet-like structures in rMVEC monoculture. In addition, diffusion of fluorescent dextran across the gel scaffold was analyzed, demonstrating that secreted proteins from the hepatocytes and MVECs can be exchanged across the gel scaffold by diffusional transport. The experimental approach described here is useful more generally for investigating microvascular networks within 3D engineered tissues with multiple cell types in vitro.

AB - Increasing interest has focused on capturing the complexity of tissues and organs in vitro as models of human pathophysiological processes. In particular, a need exists for a model that can investigate the interactions in three dimensions (3D) between epithelial tissues and a microvascular network since vascularization is vital for reconstructing functional tissues in vitro. Here, we implement a microfluidic platform to analyze angiogenesis in 3D cultures of rat primary hepatocytes and rat/human microvascular endothelial cells (rMVECs/hMVECs). Liver and vascular cells were cultured on each sidewall of a collagen gel scaffold between two microfluidic channels under static or flow conditions. Morphogenesis of 3D hepatocyte cultures was found to depend on diffusion and convection across the nascent tissue. Furthermore, rMVECs formed 3D capillary-like structures that extended across an intervening gel to the hepatocyte tissues in hepatocyter-MVEC coculture while they formed 2D sheet-like structures in rMVEC monoculture. In addition, diffusion of fluorescent dextran across the gel scaffold was analyzed, demonstrating that secreted proteins from the hepatocytes and MVECs can be exchanged across the gel scaffold by diffusional transport. The experimental approach described here is useful more generally for investigating microvascular networks within 3D engineered tissues with multiple cell types in vitro.

KW - Microfluidics

KW - Tissue engineering

KW - Vascularization

UR - http://www.scopus.com/inward/record.url?scp=68549115534&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68549115534&partnerID=8YFLogxK

U2 - 10.1096/fj.08-122820

DO - 10.1096/fj.08-122820

M3 - Article

C2 - 19246488

AN - SCOPUS:68549115534

VL - 23

SP - 2155

EP - 2164

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 7

ER -