Publications

@article{Gajera2023-kn,

title = {In vitro and in vivo assays for testing retinoids effect on 

 intestinal progenitors' lineage commitments},

author = {Krishna R Gajera and Kathryn L Fair and Gordon W Moran and Nicholas R F Hannan and Joerg Huelsken and Paloma Ord\'{o}\~{n}ez-Mor\'{a}n},

year  = {2023},

date = {2023-01-01},

journal = {Methods Mol. Biol.},

volume = {2650},

pages = {53\textendash61},

abstract = {The intestine consists of epithelial cells surrounded by a 

 complex environment as mesenchymal cells and the gut microbiota. 

 With its impressive stem cell regeneration capability, the 

 intestine is able to constantly replenish cells lost through 

 apoptosis or abrasion by food passing through. Over the past 

 decade, researchers have identified signaling pathways involved 

 in stem cell homeostasis such as retinoids pathway. Retinoids are 

 also involved in cell differentiation of healthy and cancer 

 cells. In this study, we describe several approaches in vitro and 

 in vivo to further investigate the effect of retinoids on stem 

 cells, progenitors, and differentiated intestinal cells.},

keywords = {Absorptive, Differentiation, Intestine, Organoids, Retinoids, Secretory, Stem cells},

pubstate = {published},

tppubtype = {article}

}

@article{Kirkham2020-gg,

title = {Localized induction of gene expression in embryonic stem cell 

 aggregates using holographic optical tweezers to create 

 biochemical gradients},

author = {Glen R Kirkham and James Ware and Thomas Upton and Stephanie Allen and Kevin M Shakesheff and Lee Dk Buttery},

year  = {2020},

date = {2020-01-01},

journal = {Regen. Eng. Transl. Med.},

volume = {6},

number = {3},

pages = {251\textendash261},

publisher = {Springer Science and Business Media LLC},

abstract = {Three-dimensional (3D) cell models that mimic the structure and 

 function of native tissues are enabling more detailed study of 

 physiological and pathological mechanisms in vitro. We have 

 previously demonstrated the ability to build and manipulate 3D 

 multicellular microscopic structures using holographic optical 

 tweezers (HOTs). Here, we show the construction of a precisely 

 patterned 3D microenvironment and biochemical gradient model 

 consisting of mouse embryoid bodies (mEBs) and polymer 

 microparticles loaded with retinoic acid (RA), embedded in a 

 hydrogel. We demonstrate discrete, zonal expression of the 

 RA-inducible protein Stra8 within mEBs in response to release of 

 RA from polymer microparticles, corresponding directly to the 

 defined 3D positioning of the microparticles using HOTs. These 

 results demonstrate the ability of this technology to create 

 chemical microgradients at definable length scales and to 

 elicit, with fidelity and precision, specific biological 

 responses. This technique can be used in the study of in vitro 

 microenvironments to enable new insights on 3D cell models, 

 their cellular assembly, and the delivery of drug or biochemical 

 molecules for engineering and interrogation of functional and 

 morphogenic responses. Graphical abstract.},

keywords = {Embryoid bodies, Embryonic stem cells, HOTs, In vitro model, Optical tweezers, Retinoic acid, Stem cells, Stra 8},

pubstate = {published},

tppubtype = {article}

}

@article{Ashworth2020-so,

title = {Peptide gels of fully-defined composition and mechanics for 

 probing cell-cell and cell-matrix interactions in vitro},

author = {J C Ashworth and J L Thompson and J R James and C E Slater and S Pijuan-Galit\'{o} and K Lis-Slimak and R J Holley and K A Meade and A Thompson and K P Arkill and M Tassieri and A J Wright and G Farnie and C L R Merry},

year  = {2020},

date = {2020-01-01},

journal = {Matrix Biol.},

volume = {85-86},

pages = {15\textendash33},

publisher = {Elsevier BV},

abstract = {Current materials used for in vitro 3D cell culture are often 

 limited by their poor similarity to human tissue, batch-to-batch 

 variability and complexity of composition and manufacture. Here, 

 we present a ``blank slate'' culture environment based on a 

 self-assembling peptide gel free from matrix motifs. The gel can 

 be customised by incorporating matrix components selected to 

 match the target tissue, with independent control of mechanical 

 properties. Therefore the matrix components are restricted to 

 those specifically added, or those synthesised by encapsulated 

 cells. The flexible 3D culture platform provides full control 

 over biochemical and physical properties, allowing the impact of 

 biochemical composition and tissue mechanics to be separately 

 evaluated in vitro. Here, we demonstrate that the peptide gels 

 support the growth of a range of cells including human induced 

 pluripotent stem cells and human cancer cell lines. Furthermore, 

 we present proof-of-concept that the peptide gels can be used to 

 build disease-relevant models. Controlling the peptide gelator 

 concentration allows peptide gel stiffness to be matched to 

 normal breast (1 kPa), with higher stiffness favouring the 

 viability of breast cancer cells over normal breast cells. In 

 parallel, the peptide gels may be modified with matrix 

 components relevant to human breast, such as collagen I and 

 hyaluronan. The choice and concentration of these additions 

 affect the size, shape and organisation of breast epithelial 

 cell structures formed in co-culture with fibroblasts. This 

 system therefore provides a means of unravelling the individual 

 influences of matrix, mechanical properties and cell-cell 

 interactions in cancer and other diseases.},

keywords = {biomaterials, Cancer, extracellular matrix, Stem cells, Stiffness},

pubstate = {published},

tppubtype = {article}

}