The day started with a flagship lecture from Francesco Saverio Tedesco from UCL entitled “Reprogramming human skeletal muscle (re)generation”. He talked about his group’s work combining gene and cell therapy to treat muscular dystrophies. The Dystrophin gene is large, and commonly mutated, so they have been investigating using a Human artificial chromosome to deliver dystrophin into target cells. Transplantation into mice has led to positive outcomes. The group are also working towards improved models of human muscle, generating a 3D human induced pluripotent stem (iPS) cell-derived artificial skeletal muscle combining the different component cell types, recently described in Cell Reports. They are keen to further functionalise the system by generating vascular networks and connections to motor neurons.
The first couple of short talks came from Luigi Ombrato from the Crick, who talked about Cancer associated parenchymal cells as a new component of the lung metastatic niche with stem cell features and Tiago Luis from Imperial, who has recently set up his own lab, and who talked about how perivascular niche cells sense thrombocytopenia and activate platelet-biased human stem cells in an IL-1 dependent manner. He won first prize in the oral presentations category for his talk.
Francesca Spagnoli from King’s College talked about her investigations of cell lineage restriction during the differentiation of cells into the pancreatic and liver lineages. Periklis (Laki) Pantazis from Imperial spoke about the challenges when imaging embryos due to their rotational and spatial drift. He has developed Primed Track with colleagues, which uses primed conversion of photoconvertible proteins to facilitate high-fidelity lineage tracing in mouse pre-implantation embryos, recently published in eLife. Nicolas Marichal from King's College London talked about his work on direct glia to neuron reprogramming in vivo. Luca Biasco from UCL talked about tracking human haematopoiesis at a single cell level. Their forthcoming paper in Nature Communications uses magnetic enrichment and flow cytometric sorting to separate out different cell populations that are then analysed by RNAseq.
After lunch we moved onto talks covering disease modelling and tissue engineering. Paola Bonfanti from the Crick talked about decellularising the oesophagus, seeding with muscle precursor and epithelial cells and transplanting to animal models, described in detail in Nature Communications. She moved on to talk about the thymus and discussed how to repopulate a decellularised thymus.
Ann-Sofie Thorsen from the Cambridge CRUK Institute gave a fascinating talk about characterising stem cell behaviour in KRasG12D pro-oncogenic fields of the mouse intestine. These fields are not cancerous but the cells contain a mutation in K-Ras, a gene commonly mutated in colorectal cancer. Lucy Brooks from University College went on to talk about her work on glioblastoma. Glioma stem cells are known to be responsible for the high rate of relapse and she is looking at behaviour of stem and tumour cells in different parts of the brain. She won the second prize for an oral presentation for her talk.
Molly Stevens from Imperial College talked about some examples of results from her groups work investigating how cells and proteins interact with materials. Recently her group and collaborators have carried out microscopy of bone, to show and understand the hierarchy of bone structure and the interactions between organic and inorganic components, published in Science. She talked about modulating the epithelial to mesenchymal transition in embryonic stem cells with laminin, a component of the extracellular matrix, published in PNAS. They have also developed live cell Raman spectroscopy to track cell differentiation over time. More recently they have developed Single Particle Automated Raman Trapping Analysis (SPARTA) to analyse nanoparticles, described in Nature Communications. Patient derived exosomes are very heterogeneous and this methodology enables individual exosomes to be investigated.
Molly also reiterated the importance of culture surface on the growth of stem cells, for example that the control of cell shape can influence how cells differentiate. For example, if stem cells grow as a circle there is a greater propensity to differentiation to adipocytes, whereas if coaxed to growth as a triangle or square, more osteogenic lineages are derived. They are using a focussed ion beam to investigate the interface between cells and the growth substrate. She finished by showing some results from growing cells on nanoneedles, which can be used both to deliver to and sample the contents of cells.
In the final session we moved onto applications closer to the clinic. Ana Da Silva Gomes from The Crick talked about the CLEVAR clinical trial which will start shortly and study bone marrow vascular leakiness in AML patients by Dynamic contract enhanced – MRI (DCE-MRI). Richard Jabbour from Imperial talked about treating an animal model of heart failure with hiPSC-Cardiomyocytes in a 3D fibrin based matrix.
The talks closed with a Keynote from David Scadden from Harvard who talked about their work depleting cells from the osteocyte lineage in bone marrow and investigating the consequences. He talked about using a cell instructive biomaterial that could facilitate formation of bone, including bone marrow, in vivo.
I should also give a special mention to the poster prize winner, Peter Harley, from Kings who presented an approach to model the neuro muscular junction. The day ended with a drinks reception and live music.