By Davide Danovi – Director, HipSci Cell Phenotyping Programme, Centre for Stem Cells and Regenerative Medicine, King’s College London
All cells in our body came from one original cell – a fertilised egg. A blood cell and a nerve may look very different, yet they actually share the same DNA information. Special characteristics are obtained by ‘highlighting’ parts of their genomes to be made more active, and others idle. Nonetheless, some of our cells can make exact copies of themselves (self-renewal) or become specialised, performing a specific function (differentiation). These are stem cells, the cells we study at the Centre for Stem Cells and Regenerative Medicine at King’s College London. Self-renewal and differentiation are thus the two defining features of stem cells. Stem cells can do both – we joke that it’s a bit like managing a family and a career.
Understanding our cells
In order to understand cells’ behaviour, scientists have been taking pictures of them under microscopes for a long time. In recent times, computers have joined forces with microscopes, helping us to make sense of imaging data. This means we can now try to unravel the mysteries of the shapes of our cells. How a cell looks, moves and divides – how is this shaped by signals it received from its culture conditions? How much of it is down to the genetic background of the volunteer who donated it? Now imagine a dedicated team of experts in stem cell biology, image analysis and artificial microenvironments, working with other scientists to try and answer these questions.
Well, you’ve just pictured the ‘Stem Cell Hotel’, a project supported through our NIHR Guy’s and St Thomas’ Biomedical Research Centre.
In our laboratories high up in Guy’s Tower, next to the Shard, we help visiting scientists find out more about their experiments, hosting both the users and the cells they carry. We make sure the cells are welcome, fed and imaged, as important guests. The scientists who brought them to us can access our devices, deploy tailored characterisation methods, develop assays and perform experiments. We can help them phenotype the cells – and predict their characteristics from their genetics. The assistance we provide ranges from a single room for one – simple acquisition of microscopy images, to the presidential suite – data analysis and integration to scientific collaborations such as co-development of software with technology providers. Like any hotel, our cost models vary accordingly.
This innovative, collaborative phenotyping space combines elements of a research facility, and of a research and development incubator. While serving internal and external scientists, it is able to accommodate contract-research activities where intellectual property (IP) remains with the user, unless when significant input from our scientists is required.
The Stem Cell Hotel has been an enabling feature of the Centre for Stem Cells and Regenerative Medicine that has grown together with it as their history intertwined. Professor Fiona Watt, Director of the Centre for Stem Cells and Regenerative Medicine commented: “Under Davide Danovi’s leadership, the Stem Cell Hotel has grown from concept to reality – it is exciting to see how many collaborations are already underway, or in the planning phase.”
The Centre was inaugurated in December 2015 and the Stem Cell Hotel has moved on a long way since, and is now fully operational. Created within the framework of the Human Induced Pluripotent Stem Cell Initiative (HIPSCI), it leverages expertise from several leading edge research projects which are ongoing at the Centre, on different cell types.
From a personal perspective, I am privileged to be leading a team of scientists with expertise in high content and high throughput analysis and data integration. One of the most exciting things about this work is the collaboration and the impact it has on a diverse multidisciplinary community of scientists. We have genuinely become a meeting point for university and biotechnology companies. We host scientists from a range of different disciplines and backgrounds including clinical, translational and industrial who all have their own take on stem cells. It’s illuminating to hear different perspectives, and this allows us, like the cells we study, to be flexible in what we do.
Turning back the clock
Imagine bringing one specialised cell back into an embryonic-like stage so that it can again become any type of cell. This Nobel-prize winning technology is referred to as reprogramming cells into ‘induced pluripotent stem cells’.
One recent example of the power of this approach is our study detailing the characterisation of a panel of 110 human induced pluripotent stem cell lines from 75 individual volunteers. We looked for cells behaving in an unusual way and were able to associate these unusual behaviours with single changes in a nucleotide, a letter of their DNA code. Data, including raw images from this study have been published to open access repositories, granting the wider scientific community access and the ability to replicate the analysis. Scientists can now access specific cell lines with particular genomic characteristic or even a particular shape. This open science project is at the cross-road between databases with information about biological models (genes, proteins, etc) and biobanks of human samples. The impact comes here from the ability to define criteria to ‘benchmark’ or quality control cells based on these analysis methods.
We have also recently published another study as a collaboration between our team of scientists at the Stem Cell Hotel and experts on endothelial cells. Endothelial cells are the cells that line the interior of our blood vessels and the vessels in our lymphatic system. Characterising these cells, and understanding how they differ when derived from different sources could help us find new ways to obtain the right vessels for tissue engineering for specific organs.
In parallel, we compared two cell types: endothelial cells forming colonies derived from induced pluripotent stem cells (iPSC-ECFC) alongside primary human umbilical vein endothelial cells (HUVEC). We have derived information on the cells’ shape and form, and how they interact with each other in order to capture differences between cell populations. This approach exemplifies an important yet simple strategy to benchmark endothelial cells in different conditions, and to assist in development of new tools for biological research and regenerative medicine applications.
Born from boldly translational research embracing the spirit of open innovation, the Stem Cell Hotel grants access to state-of-the-art technology for stem cell biology, high content analysis and artificial microenvironments. Its highly collaborative environment serves communities centred around academic, clinical, and commercial research.