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Fibrin-based 3D matrices induce angiogenic behavior of adipose-derived stem cells.

ABSTRACT: Engineered three-dimensional biomaterials are known to affect the regenerative capacity of stem cells. The extent to which these materials can modify cellular activities is still poorly understood, particularly for adipose-derived stem cells (ASCs). This study evaluates PEGylated fibrin (P-fibrin) gels as an ASC-carrying scaffold for encouraging local angiogenesis by comparing with two commonly used hydrogels (i.e., collagen and fibrin) in the tissue-engineering field. Human ASCs in P-fibrin were compared to cultures in collagen and fibrin under basic growth media without any additional soluble factors. ASCs proliferated similarly in all gel scaffolds but showed significantly elongated morphologies in the P-fibrin gels relative to other gels. P-fibrin elicited higher von Willebrand factor expression in ASCs than either collagen or fibrin while cells in collagen expressed more smooth muscle alpha actin than in other gels. VEGF was secreted more at 7 days in fibrin and P-fibrin than in collagen and several other angiogenic and immunomodulatory cytokines were similarly enhanced. Fibrin-based matrices appear to activate angiogenic signaling in ASCs while P-fibrin matrices are uniquely able to also drive a vessel-like ASC phenotype. Collectively, these results suggest that P-fibrin promotes the angiogenic potential of ASC-based therapeutic applications.

SUBMITTER: Chung E

PROVIDER: S-EPMC4380681 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Fibrin-based 3D matrices induce angiogenic behavior of adipose-derived stem cells.

Chung Eunna E Rytlewski Julie A JA Merchant Arjun G AG Dhada Kabir S KS Lewis Evan W EW Suggs Laura J LJ

Acta biomaterialia 20150116

Engineered three-dimensional biomaterials are known to affect the regenerative capacity of stem cells. The extent to which these materials can modify cellular activities is still poorly understood, particularly for adipose-derived stem cells (ASCs). This study evaluates PEGylated fibrin (P-fibrin) gels as an ASC-carrying scaffold for encouraging local angiogenesis by comparing with two commonly used hydrogels (i.e., collagen and fibrin) in the tissue-engineering field. Human ASCs in P-fibrin wer ...[more]

PMID: 25600400

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Project description:PurposeWe previously reported that fibroblasts migrating within 3-D collagen matrices move independently, whereas fibroblasts within 3-D fibrin matrices form an interconnected network. Similar networks have been identified previously during in vivo corneal wound healing. In this study, we investigate the role of fibronectin in mediating this mechanism of collective cell spreading, migration and patterning.MethodsTo assess cell spreading, corneal fibroblasts were plated within fibrillar collagen or fibrin matrices. To assess migration, compacted cell-populated collagen matrices were nested inside cell-free fibrin matrices. Constructs were cultured in serum-free media containing PDGF, with or without RGD peptide, anti-α5 or anti-fibronectin blocking antibodies. In some experiments, LifeAct and fluorescent fibronectin were used to allow dynamic assessment of cell-induced fibronectin reorganization. 3-D and 4-D imaging were used to assess cell mechanical behavior, connectivity, F-actin, α5 integrin and fibronectin organization.ResultsCorneal fibroblasts within 3-D fibrin matrices formed an interconnected network that was lined with cell-secreted fibronectin. Live cell imaging demonstrated that fibronectin tracks were formed at the leading edge of spreading and migrating cells. Furthermore, fibroblasts preferentially migrated through fibronectin tracks laid down by other cells. Interfering with cell-fibronectin binding with RGD, anti α5 integrin or anti fibronectin antibodies inhibited cell spreading and migration through fibrin, but did not affect cell behavior in collagen.ConclusionsIn this study, a novel mode of cell patterning was identified in which corneal fibroblasts secrete and attach to fibronectin via α5β1 integrin to facilitate spreading and migration within 3-D fibrin matrices, resulting in the formation of localized fibronectin tracks. Other cells use these fibronectin tracks as conduits, resulting in an interconnected cell-fibronectin network.

Dataset Information

Fibrin-based 3D matrices induce angiogenic behavior of adipose-derived stem cells.

Publications

Fibrin-based 3D matrices induce angiogenic behavior of adipose-derived stem cells.

Similar Datasets

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