Our 5th year of Science on Tap continues!

Thanks to the continued support of UNM, Explora and the National Museum of Nuclear Science and History

 

 A time to eat, drink & talk about science!

on Central is our new home 

Join us Thursday, May 4 at 5:30!

 

 Testable You: Bioengineering approaches to personalised medicine

 

The conventional approach to cell culture uses 2D surfaces to attach and grow cells on tissue culture polystyrene. These systems are used to examine the fundamental biological pathways of disease, evaluate the cytotoxicity of biomaterials, explore biochemical pathways and model wound healing (to name just a few). While these systems are central to much of our current research, it is well established that they fail to reproduce many of the cell-cell signalling and external cues experienced by cells in tissue (1) Research over the last 5-10 years has shown that cell behaviour in 2D varies significantly from that in 3D, with variations in cell shape, gene profile and migration behaviour to name a few. (2, 3) Critically have restricted lifespans making it difficult to undertake long-term studies (4). 

At the other end of the testing spectrum we have a wide range of animal models which are currently the gold standard for drug and medical devices evaluation. Increasingly it is becoming clear that many animal models do not correlate well with specific disease states. (3) While humanised mouse models are developing rapidly, (5), there is an increasing movement internationally towards replacing, reducing and refining animal testing including the EU Directive on the protection of animals used for scientific purposes (EU Directive 2010/63/EU).

It is clear that we need new approaches for cell culture that replicate the cell microenvironment, are easily manipulated to address specific research questions or target specific pathways. The systems need to be reproducible, scalable and critically validated against the gold standards. One of the most popular current approaches is the spheroid. Used to replicate tumour structures and a range of other tissues (4), part of their attraction in the flexibility they enable when created from stem cells. (6) The alternative to the spheroid is a scaffold based model. Based on tissue engineering knowledge, these systems use both synthetic and natural materials to create a 3D framework to support cell attachment and growth. Examples include tissue engineered skin models built around decellurised tissue or collagen-1 (7).  Interestingly it is only recently that any of these models have started to integrate inflammatory or infection pathways. (2, 8) This is particularly critical for toxicity testing and disease models where inflammatory cells play a critical role secreting proteases, cytokines, growth factors and other allogeneic substances. (2).

This talk will discuss the range of methods currently being used to develop personalised testing systems for Medical and Health Technologies.

1.   Alépée N. State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology. Altex. 2014.

2.   Carvalho MR, Lima D, Reis RL, Correlo VM, Oliveira JM. Evaluating Biomaterial- and Microfluidic-Based 3D Tumor Models. Trends Biotechnol. 2015;33(11):667-78.

3.   Hutmacher DW, Holzapfel BM, De-Juan-Pardo EM, Pereira BA, Ellem SJ, Loessner D, et al. Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance. Current Opinion in Biotechnology. 2015;35:127-32.

4.   Wrzesinski K, Magnone MC, Hansen LV, Kruse ME, Bergauer T, Bobadilla M, et al. HepG2/C3A 3D spheroids exhibit stable physiological functionality for at least 24 days after recovering from trypsinisation. Toxicol Res-Uk. 2013;2(3):163-72.

5.   Shultz LD, Brehm MA, Garcia-Martinez JV, Greiner DL. Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol. 2012;12(11):786-98.

6.   Villasante A, Vunjak-Novakovic G. Tissue-engineered models of human tumors for cancer research. Expert Opinion on Drug Discovery. 2015;10(3):257-68.

7.   Linde N, Gutschalk CM, Hoffmann C, Yilmaz D, Mueller MM. Integrating Macrophages into Organotypic Co-Cultures: A 3D In Vitro Model to Study Tumor-Associated Macrophages. Plos One. 2012;7(7).

8.   Chau DYS, Johnson C, MacNeil S, Haycock JW, Ghaemmaghami AM. The development of a 3D immunocompetent model of human skin. Biofabrication. 2013;5(3).