Kunz-Schughart, Leoni A. and Schroeder, Josef A. and Wondrak, Marit and Van Rey, Frank and Lehle, Karla and Hofstaedter, Ferdinand and Wheatley, Denys N. (2006) Potential of fibroblasts to regulate the formation of three-dimensional vessel-like structures from endothelial cells in vitro. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 290 (5). C1385-C1398. ISSN 0363-6143, 1522-1563
Full text not available from this repository. (Request a copy)Abstract
The development of vessel-like structures in vitro to mimic as well as to realize the possibility of tissue-engineered small vascular networks presents a major challenge to cell biologists and biotechnologists. We aimed to establish a three-dimensional (3-D) culture system with an endothelial network that does not require artificial substrates or ECM compounds. By using human skin fibroblasts and endothelial cells (ECs) from the human umbilical vein (HUVECs) in diverse spheroid coculture strategies, we verified that fibroblast support and modulate EC migration, viability, and network formation in a 3-D tissue-like stromal environment. In mixed spheroid cultures consisting of human ECs and fibroblasts, a complex 3-D network with EC tubular structures, lumen formation, pinocytotic activity, and tight junction complexes has been identified on the basis of immunohistochemical and transmission electron microscopic imaging. Tubular networks with extensions up to 400 mu m were achieved. When EC suspensions were used, EC migration and network formation were critically affected by the status of the fibroblast. However, the absence of EC migration into the center of 14-day, but not 3-day, precultured fibroblast spheroids could not be attributed to loss of F viability. In parallel, it was also confirmed that migrated ECs that entered cluster-like formations became apoptotic, whereas the majority of those forming vessel-like structures remained viable for > 8 days. Our protocols allow us to study the nature of tubule formation in a manner more closely related to the in vivo situation as well as to understand the basis for the integration of capillary networks in tissue grafts and develop methods of quantifying the amount of angiogenesis in spheroids using fibroblast and other cells isolated from the same patient, along with ECs.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SMOOTH-MUSCLE CELLS; COCULTURE MODEL; MULTICELLULAR SPHEROIDS; ANGIOGENESIS INHIBITORS; ANTIANGIOGENIC THERAPY; RHEUMATOID-ARTHRITIS; SPROUT FORMATION; LUMEN FORMATION; TUMOR BIOLOGY; BLOOD-VESSELS; endothelium; angiogenesis; human umbilical vein endothelial cell; multicellular spheroid; coculture; tubular structures |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Feb 2021 11:06 |
| Last Modified: | 15 Feb 2021 11:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34551 |
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