Effects of Extracellular Matrix Density and Mesenchymal Stem Cells on Neovascularization In Vivo

Aberrant angiogenesis is common to a variety of diseases in which alterations in tissue mechanical properties also occur. A fundamental understanding of the interdependence of angiogenesis and tissue structural properties may enhance the development of therapeutic strategies. We previously establish...

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Bibliographic Details
Published in:Tissue engineering. Part A 2011-04, Vol.17 (7-8), p.95-914
Main Authors: Kniazeva, Ekaterina, Kachgal, Suraj, Putnam, Andrew J.
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Cell Culture Techniques
Cell Differentiation - physiology
Cell Line
Extracellular matrix
Extracellular Matrix - metabolism
Fibrin
Humans
Immunohistochemistry
Male
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - physiology
Mice
Neovascularization
Neovascularization, Physiologic - physiology
Original
Original Articles
Physiological aspects
Properties
Stem cells
Tissue engineering
Veins & arteries
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Summary:Aberrant angiogenesis is common to a variety of diseases in which alterations in tissue mechanical properties also occur. A fundamental understanding of the interdependence of angiogenesis and tissue structural properties may enhance the development of therapeutic strategies. We previously established that increasing extracellular matrix density inhibits capillary morphogenesis in three-dimensional tissues in vitro , and that addition of human mesenchymal stem cells (MSCs) partially rescues a healthy angiogenic phenotype. This study's goal was to investigate if these effects can be recapitulated in vivo. Human umbilical vein endothelial cells, MSCs, or a mixture of both was suspended in fibrin gel precursor solutions of 5, 10, and 15 mg/mL concentrations and injected subcutaneously into SCID mice. Neovascularization was assessed in tissue constructs retrieved at 3, 7, and 21 days by quantifying vessel numbers, perfusion, thickness, maturity, and perivascular collagen deposition. The data show that changing extracellular matrix density inhibits capillary morphogenesis in vivo in a manner consistent with that observed in vitro. Delivery of both human umbilical vein endothelial cells and MSCs produced more robust and mature vessels than delivery of either cell type alone in all tissue concentrations.
ISSN:1937-3341
1937-335X
DOI:10.1089/ten.tea.2010.0275