Cell-substrate interactions 3 Flashcards
What are the benefits of scaffolds/ECM for stem cell therapy
Provides path and direction for the cells to grow and develop.
These can be synthetic or naturally occurring ECM
What can the substrate these mesenchymal cells are in do
Change the development to a different type of cell e.g. osteoblasts instead of fibroblasts.
What property of the scaffold can help differentiate mesenchymal cells
The stiffness.
Give some methods of these cells to cause adhesion to the scaffold surface
Protein adsorption
Linear RGD tripeptide
Linear RGD tripeptide with spacer
Cyclic RGD pentapeptide
How can the cell structure be modified for cell differentiation
Different surface receptors can initiate different lineages of cells as they react differently with the scaffold
What is nanotopography and what use does it have in MSC differentiation
Nanotopography refers to specific surface features which form or are generated at the nanoscopic scale - essentially changing shape or adding holes in ECM which can promote cell differentiation as is simulates in vivo.
What is geometric confinement and how is it used in stem cells
Reducing the same that cells can grow in can allow them to differentiate differently.
In summary, give the 4 ways that ECM scaffolds can be manipulated to promote specific cell growth and differentiation
Surface immobilised biosignals e.g. peptides
Nanotopography
Stiffness of substrate
Geometric confinement
Influenced by the natural ECM required to produce desired cell type.
Give some examples of nanotopography materials
WIDER READING - Wang et al 2016
Nanogrooves
Nanofibres
Nanopillars
Porous silicon
How can a random surface nanoroughness be formed in nanotopography and why is this important
Wider reading - S.lavenus et al 2015
Via acid or alkali etching which results increases in adhesion, proliferation and/or differentation of human MSCs
Where have nanotopographies been applied clinically
WIDER READING - Kim et al 2014
Used as cell patches for tissue regeneration - nanogrooves on biodegradable PLGA film with human bone marrow stromal cells
With regards to human embryonic stem cells what was discovered using nanotopography
WIDER READING - Gerecht S 2007
Cultured human ESCs on a nanoscale line-grating resulted in more HESC alignment and elongation compared to flat surfaces. This allowed further experimentation to reveal that the cytoskeleton relies on actin polymerization for HESCs by exposing these cells to actin distrupting agents.
What effect did nanotopography have on neural cells
WIDER READING - FAN 2002
Used different roughness of topography of silicon which significantly increased cell adhesion and viability.
What happens to mesenchymal stem cells when cultured on soft substrates
Wider reading - Gerardo 2019
Closer resemblance to pleuripotent stem cells - more relaxed nuclei, focal adhesions and F-actin assembling also more expressed pluripotent genes.
What happened to mesenchymal stem cells with TGF-beta on a stiff matrix
WIDER READING - Park 2012
Exposed MSC to TGF-beta to try and turn them into smooth muscle cells.
In comparison to soft substrates, stiff surfaces had - higher SMC marker expression (alpha-actin)
