Complex temporal regulation of capillary morphogenesis by fibroblasts
| Autor: | Swathi Balaji, Daria A. Narmoneva, Jennifer R. Hurley |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cell signaling
Stromal cell Time Factors Physiology Angiogenesis Morphogenesis Neovascularization Physiologic Cell Communication Extracellular Matrix Cell Interactions Biology Extracellular matrix Cell–cell interaction medicine Humans Fibroblast Cells Cultured Skin Cell Biology Fibroblasts Coculture Techniques Cell biology Capillaries Endothelial stem cell medicine.anatomical_structure Immunology Endothelium Vascular |
| Zdroj: | American journal of physiology. Cell physiology. 299(2) |
| ISSN: | 1522-1563 |
| Popis: | Interactions between endothelial and stromal cells are important for vascularization of regenerating tissue. Fibroblasts (FBs) are responsible for expression of angiogenic growth factors and matrix metalloproteinases, as well as collagen deposition and fibrotic myocardial remodeling. Recently, self-assembling peptide nanofibers were described as a promising environment for cardiac regeneration due to its synthetic nature and control over physiochemical properties. In this study, peptide nanofibers were used as a model system to quantify the dual role of fibroblasts in mediating angiogenesis chemically via expression of angiogenic factors and mechanically via cell-mediated scaffold disruption, extracellular matrix deposition, and remodeling. Human microvascular endothelial cells (ECs), FBs, or cocultures were cultured in three-dimensional nanofibers for up to 6 days. The peptide nanofiber microenvironment supported cell migration, capillary network formation, and cell survival in the absence of detectable scaffold contraction and proteolytic degradation. FBs enhanced early capillary network formation by “assisting” EC migration and increasing vascular endothelial growth factor and Angiopoietin-1 expression in a temporal manner. EC-FB interactions attenuated FB matrix metalloproteinase-2 expression while increasing collagen I deposition, resulting in greater construct stiffness and a more stable microenvironment in cocultures. Whereas FBs are critical for initial steps of angiogenesis in the absence of external angiogenic stimulation, coordinated efforts by ECs and FBs are required for a balance between cell-mediated scaffold disruption, extracellular matrix deposition, and remodeling at later time points. The findings of this study also emphasize the importance of developing a microenvironment that supports cell-cell interactions and cell migration, thus contributing toward an optimal environment for successful cardiac regeneration strategies. |
| Databáze: | OpenAIRE |
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