Engineering Blood and Lymphatic Microvascular Networks in Fibrin Matrices

被引：64

作者：

Knezevic L. ^{[1
,2
,3
]}

Schaupper M. ^{[1
,2
]}

Mühleder S. ^{[1
,2
]}

Schimek K. ^{[4
,5
]}

Hasenberg T. ^{[5
]}

Marx U. ^{[5
]}

Priglinger E. ^{[1
,2
]}

Redl H. ^{[1
,2
]}

Holnthoner W. ^{[1
,2
]}

机构：

[1] Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna

[2] Austrian Cluster for Tissue Regeneration, Vienna

[3] Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht

[4] Technische Universität Berlin, Medical Biotechnology, Berlin

[5] TissUse GmbH, Berlin

来源：

Holnthoner, Wolfgang (wolfgang.holnthoner@trauma.lbg.ac.at) | 1600年 / Frontiers Media S.A., c/o Michael Kenyon, ch. de la Pecholettaz 6, Epalinges, 1066, Switzerland卷 / 05期

关键词：

Coculture; Endothelial cells; Fibrin; Lymphatics; Tissue engineering;

D O I：

10.3389/fbioe.2017.00025

中图分类号：

学科分类号：

摘要：

Vascular network engineering is essential for nutrient delivery to tissue-engineered constructs and, consequently, their survival. In addition, the functionality of tissues also depends on tissue drainage and immune cell accessibility, which are the main functions of the lymphatic system. Engineering both the blood and lymphatic microvasculature would advance the survival and functionality of tissue-engineered constructs. The aim of this study was to isolate pure populations of lymphatic endothelial cells (LEC) and blood vascular endothelial cells (BEC) from human dermal microvascular endothelial cells and to study their network formation in our previously described coculture model with adipose-derived stromal cells (ASC) in fibrin scaffolds. We could follow the network development over a period of 4 weeks by fluorescently labeling the cells. We show that LEC and BEC form separate networks, which are morphologically distinguishable and sustainable over several weeks. In addition, lymphatic network development was dependent on vascular endothelial growth factor (VEGF)-C, resulting in denser networks with increasing VEGF-C concentration. Finally, we confirm the necessity of cell-cell contact between endothelial cells and ASC for the formation of both blood and lymphatic microvascular networks. This model represents a valuable platform for in vitro drug testing and for the future in vivo studies on lymphatic and blood microvascularization. © 2017 Knezevic, Schaupper, Mühleder, Schimek, Hasenberg, Marx, Priglinger, Redl and Holnthoner.

引用

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