PUBLICATION

Artificial cell membrane binding thrombin constructs drive in situ fibrin hydrogel formation

Authors
Deller, R.C., Richardson, T., Richardson, R., Bevan, L., Zampetakis, I., Scarpa, F., Perriman, A.W.
ID
ZDB-PUB-190614-1
Date
2019
Source
Nature communications   10: 1887 (Journal)
Registered Authors
Richardson, Rebecca
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation
  • Cell Engineering/methods*
  • Cell Membrane/chemistry*
  • Cell Membrane/metabolism
  • Disease Models, Animal
  • Elastic Modulus
  • Extracellular Matrix/metabolism
  • Fibrin/metabolism*
  • Fibroblasts
  • Humans
  • Hydrogels/chemistry
  • Hydrogels/metabolism
  • Mesenchymal Stem Cells
  • Polymers/chemistry
  • Recombinant Proteins/chemistry
  • Recombinant Proteins/genetics
  • Recombinant Proteins/metabolism
  • Surface-Active Agents/chemistry
  • Thrombin/chemistry*
  • Thrombin/genetics
  • Thrombin/metabolism
  • Wound Healing*
  • Zebrafish
PubMed
31015421 Full text @ Nat. Commun.
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.
Genes / Markers
Figures
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping