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Growth factor-free salt-leached silk scaffolds for differentiating endothelial cells.

ABSTRACT: Recently, controllable kinetic assembly was introduced into the salt-leaching process with silk proteins to form scaffolds, which achieved improvement in tuning the micro-structural and mechanical properties. Here, more control of the kinetic assembly of silk in the process was integrated into salt-leaching process, resulting in significant mechanical modification of the scaffolds generated. Both glycerol additions and treatment to concentrate the protein were used to tune hydrophilic interactions during aqueous solution processing and to reduce beta-sheet formation during the salt-leaching process. These new scaffolds showed gradient changes in elastic modulus in the range of 0.9 to 7.9 kPa. Bone marrow mesenchymal stem cells grew well and showed endothelial differentiation behavior on the scaffolds with optimized stiffness. These results indicated that the introduction of silk kinetic assembly provides an additional option for the control of porous silk scaffold properties.

SUBMITTER: Xiao L

PROVIDER: S-EPMC6295658 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Growth factor-free salt-leached silk scaffolds for differentiating endothelial cells.

Xiao Liying L Zhu Caihong C Ding Zhaozhao Z Liu Shanshan S Yao Danyu D Lu Qiang Q Kaplan David L DL

Journal of materials chemistry. B 20180612 26

Recently, controllable kinetic assembly was introduced into the salt-leaching process with silk proteins to form scaffolds, which achieved improvement in tuning the micro-structural and mechanical properties. Here, more control of the kinetic assembly of silk in the process was integrated into salt-leaching process, resulting in significant mechanical modification of the scaffolds generated. Both glycerol additions and treatment to concentrate the protein were used to tune hydrophilic interactio ...[more]

PMID: 30574331

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Project description:The tumor microenvironment contains various components, including cancer cells, tumor vessels, and cancer-associated fibroblasts, the latter of which are comprised of tumor-promoting myofibroblasts and tumor-suppressing fibroblasts. Multiple lines of evidence indicate that transforming growth factor-β (TGF-β) induces the formation of myofibroblasts and other types of mesenchymal (non-myofibroblastic) cells from endothelial cells. Recent reports show that fibroblast growth factor 2 (FGF2) modulates TGF-β-induced mesenchymal transition of endothelial cells, but the molecular mechanisms behind the signals that control transcriptional networks during the formation of different groups of fibroblasts remain largely unclear. Here, we studied the roles of FGF2 during the regulation of TGF-β-induced mesenchymal transition of tumor endothelial cells (TECs). We demonstrated that auto/paracrine FGF signals in TECs inhibit TGF-β-induced endothelial-to-myofibroblast transition (End-MyoT), leading to suppressed formation of contractile myofibroblast cells, but on the other hand can also collaborate with TGF-β in promoting the formation of active fibroblastic cells which have migratory and proliferative properties. FGF2 modulated TGF-β-induced formation of myofibroblastic and non-myofibroblastic cells from TECs via transcriptional regulation of various mesenchymal markers and growth factors. Furthermore, we observed that TECs treated with TGF-β were more competent in promoting in vivo tumor growth than TECs treated with TGF-β and FGF2. Mechanistically, we showed that Elk1 mediated FGF2-induced inhibition of End-MyoT via inhibition of TGF-β-induced transcriptional activation of α-smooth muscle actin promoter by myocardin-related transcription factor-A. Our data suggest that TGF-β and FGF2 oppose and cooperate with each other during the formation of myofibroblastic and non-myofibroblastic cells from TECs, which in turn determines the characteristics of mesenchymal cells in the tumor microenvironment.

Dataset Information

Growth factor-free salt-leached silk scaffolds for differentiating endothelial cells.

Publications

Growth factor-free salt-leached silk scaffolds for differentiating endothelial cells.

Similar Datasets

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