Deller, Robert C 
ORCID: 0000-0002-5812-583X, Richardson, Thomas, Richardson, Rebecca, Bevan, Laura, Zampetakis, Ioannis, Scarpa, Fabrizio and Perriman, Adam W
(2019)
Artificial cell membrane binding thrombin constructs drive in situ fibrin hydrogel formation.
NATURE COMMUNICATIONS, 10 (1).
1887-.
|
Text
artificial cell.pdf - Published version Download (7MB) | Preview |
Abstract
Cell membrane re-engineering is emerging as a powerful tool for the development of next generation cell therapies, as it allows the user to augment therapeutic cells to provide additional functionalities, such as homing, adhesion or hypoxia resistance. To date, however, there are few examples where the plasma membrane is re-engineered to display active enzymes that promote extracellular matrix protein assembly. Here, we report on a self-contained matrix-forming system where the membrane of human mesenchymal stem cells is modified to display a novel thrombin construct, giving rise to spontaneous fibrin hydrogel nucleation and growth at near human plasma concentrations of fibrinogen. The cell membrane modification process is realised through the synthesis of a membrane-binding supercationic thrombin-polymer surfactant complex. Significantly, the resulting robust cellular fibrin hydrogel constructs can be differentiated down osteogenic and adipogenic lineages, giving rise to self-supporting monoliths that exhibit Young's moduli that reflect their respective extracellular matrix compositions.
| Item Type: | Article |
|---|---|
| Additional Information: | Cell membrane re-engineering is emerging as a powerful tool for the development of next generation cell therapies, as it allows the user to augment therapeutic cells to provide additional functionalities, such as homing, adhesion or hypoxia resistance. To date, however, there are few examples where the plasma membrane is re-engineered to display active enzymes that promote extracellular matrix protein assembly. Here, we report on a self-contained matrix-forming system where the membrane of human mesenchymal stem cells is modified to display a novel thrombin construct, giving rise to spontaneous fibrin hydrogel nucleation and growth at near human plasma concentrations of fibrinogen. The cell membrane modification process is realised through the synthesis of a membrane-binding supercationic thrombin-polymer surfactant complex. Significantly, the resulting robust cellular fibrin hydrogel constructs can be differentiated down osteogenic and adipogenic lineages, giving rise to self-supporting monoliths that exhibit Young’s moduli that reflect their respective extracellular matrix compositions. |
| Uncontrolled Keywords: | Cell Membrane, Extracellular Matrix, Fibroblasts, Mesenchymal Stem Cells, Animals, Animals, Genetically Modified, Zebrafish, Humans, Disease Models, Animal, Polymers, Thrombin, Fibrin, Recombinant Proteins, Hydrogels, Surface-Active Agents, Wound Healing, Cell Differentiation, Elastic Modulus, Cell Engineering |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 07 May 2019 08:21 |
| Last Modified: | 19 Jan 2023 00:51 |
| DOI: | 10.1038/s41467-019-09763-0 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3039512 |
Dimensions
Dimensions
