Cell models and biotechnology

Overview

The Cell Models and Biotechnology group focuses on the application of the life sciences to the fields of engineering, medicine and technology - with particular emphasis on their use in regenerative medicine and drug formulation, manufacture and delivery.

The group primarily develops accurate and biosensitive, in-vitro-in vivo-like, models of human tissues and organs through the use of cells, materials and growth factors to understand the underlying biological mechanisms involved. Specialist expertise within the group centres on the development of alternative models of the skin, eye, lung and liver. In addition, the group also considers the exploitation of novel drug delivery vehicles to enhance the therapeutic efficacy of a drug, as well as innovative techniques to aid the modulation of the biological characteristics of the cells themselves.

Ultimately, the development of these more accurate and predictive cell models play a pivotal role in the translation and assessment of drugs for safety and use in clinical practice.

What the group does

The Cell Models and Biotechnology group focuses on the in vitro model design, characterisation and validation of tissues and/or organs of interest. In addition, exploitation of these engineered models are used to assess toxicity and efficacy characteristics of novel compounds or therapeutics. Specific research interests include:

Development of advanced 3D cell culture models of (human) skin, eye, lung and liver for toxicity testing i.e. environmental and pharmaceutical
Incorporation and characterisation of stimuli-responsive cell culture models e.g. immuno-competent, perfusion-based
Characterisation and development of novel biomaterials and drug delivery carriers
Development of a desiccation-tolerant cell lines and/or addressing challenges associated with long-term storage of (human/mammalian/stem) cell lines
Optimisation of processing parameters for (large-scale) cell generation and manufacture
Development of alternative scientific methods and techniques for 3Rs research

Services offered

2D and 3D toxicity screening using advanced ocular, airway, GI and skin cell models
Development of new screening platforms and cultures that are more biologically relevant and with desired/specific endpoint parameters
Permeability modelling including transporter-mediated drug trafficking (including radiolabelled compounds)
Cell surface marker and cytokine/chemokine expression i.e. ELISA and flow cytometry
Long term cell viability assessment, characterisation and validation
Biomaterial characterisation and assessment i.e. physical/biological/rheological

Key projects

Development and Characterisation of a Novel Microphysical Systems of Human Organs
Increasing attrition rates in the pharmaceutical industry have catalysed requirements for new technologies, which can be incorporated into pre-clinical drug development to de-risk compounds pre clinic entry.
In a joint collaboration with CN Bio Innovations Ltd., the Cell Models and Biotechnology group aim to develop establish an advanced liver microphysiological systems that allows the direct interaction(s) between the liver and other organs to be accurately modelled in vitro.
Construction of a Novel Ophthalmic Cell Model for Regenerative Medicine
To ensure the development and safety aspects of new ophthalmic drugs, a variety of techniques have been used to confirm their effectiveness and/or potential harm in patients.
However, some of these techniques still rely on the use of animals or, where alternatives exist, are too basic (i.e. cannot relate or mimic what happens in the body), too costly, or simply do not provide enough information on the mechanism of drug uptake.
The aim of this research is to develop a perfusion-based, biologically representative model of the eye using ophthalmic cell lines, novel constructs and additional biomimetic materials. It is anticipated that this model may be exploited for the elucidation of cellular behaviour/mechanisms, for regenerative therapeutic applications and drug development i.e. formulation, toxicity and disease modelling.
Evaluating Biomarkers and Response of Alveolar Macrophages to Inhaled Medicines
New inhaled medicines require extensive non-clinical safety validation before progressing to the clinic for evaluation of safety and efficacy in humans. During this assessment stage, it is not uncommon for alveolar macrophage responses to be observed in histological lung slices of animals during inhalation toxicology studies: these are typically characterised by a highly vacuolated appearance and larger cell size.
This project aims to identify and characterise the reason(s), mechanism and downstream response of the presence of these (foamy) macrophages.
Processing and Formulation Engineering of Inhalable Nanoaggregates and Microparticles
Lung diseases are a major global health burden and the inhalation of therapeutic aerosols is deemed the traditional medical strategy to treat these ailments. However, achieving aerosol deposition in the lungs is a major challenge even for those patients with good inhaler technique.
This project, in collaboration with a number of industrial and academic partners, aims to predict, manufacture and assess a portable dosage form to maximise its therapeutic efficacy following delivery to the lungs
Desiccation Tolerance and long-term storage of mammalian cells for bioprocessing applications
Cells are involved in a range of biotechnological applications and more recently have been increasingly exploited in regenerative medicine. Critical to successful applications involving mammalian cells are their long-term storage and transport, for which cryopreservation in liquid nitrogen is the most frequently used strategy.
However, cryopreservation suffers from high costs, difficulties in transport logistics and the use of undesirable additives. An alternative approach, proposed as low cost, low maintenance and process-compatible, is viable desiccation of mammalian cells.
This project aims to, ultimately, develop and/or assess the feasibility of a desiccation-tolerant mammalian cell line via molecular, biological and/or bioprocessing-defined manipulation.