Pick of the posters: ISCT 2023
At this year’s Annual Meeting of The International Society for Cell and Gene Therapy (ISCT; 31 May-3 June; Paris, France), we took a trip around the poster hall and picked out some of our favorites. Check out our top 3 below.
Inter-donor differences in the secretome of umbilical cord-derived mesenchymal stromal cells correlated with differences in their in vivo immunosuppressive function
Kathryn Strange, Anthony Nolan Research Institute (London, UK), University College London (UK)
Tell us about your research
I’m currently working on umbilical cord mesenchymal stromal cells (MSCs), trying to understand their mechanism of action, what they’re secreting, and how that affects their immunosuppressive potency. In particular, I look at things like HLA-G, but also the secretome as a whole.
What is the significance of immunomodulation in terms of treatment options?
One of the main things is that within clinical trials, people notice that MSCs are very heterogeneous, meaning that they vary a lot between donors. So, something that we want to highlight is that there are various biomarkers or factors that these cells produce that could be used to identify cord MSCs that perform better in patients.
What are the short-term and long-term implications of this research?
Short-term, it’s all about understanding how the cells can be prepared before trials. That’s the most important thing. One of the big hurdles with MSCs is generally how they’re licensed or primed, how they’re prepared and how they’re administered to patients, because although there’s a lot of suggested mechanisms about how they work, there’s no definitive. There also isn’t one solution for every application, it’s very dependent on the disease you want to apply them to. So in the short term, this is all about understanding how they work and trying to establish which molecules are most important, which one needs to be used together and which ones don’t really actually matter.
In the long term, identifying the best donor for the patient.
If you had unlimited resources, what work would you do next?
I would love to do some form of genetic modification on MSCs. I’d like to highlight some things that I’ve found as potential biomarkers, translate them to MSCs or make them super potent for that biomarker and then apply it to everything.
Three-dimensional cultured dissociated mesenchymal stromal cells mitigate in vitro neutrophil extracellular traps induced by lipopolysaccharide
Juliana Borges Vieira, Federal University of Rio de Janeiro (Brazil)
Tell us about your research
My research is about neutrophil extracellular traps (NETs), aiming to investigate a new treatment for excessive NET release. We’re exploring the use of mesenchymal stem cells in two different types of culture systems: two-dimensional culture and three-dimensional culture. In summary, we observed that only the MSCs submitted to 3D conditions were able to reduce the NET release. The 2D MSCs were not able to reduce in a significant way the NET release. So that’s the main point.
What are the next steps for your research?
Our next steps involve exploring the mechanisms of action of these 3d-cultured MSCs. We’re investigating whether these cells exhibit autophagy behavior, which is our next focus. We hypothesize that MSCs in 3D culture induce autophagy, which could explain why they effectively reduce NET release compared to 2D-cultured MSCs.
If you had unlimited resources, what work would you do?
It’s a big step and would take time but initiating a clinical study comparing the effects of MSCs from 2D and 3D cultures. I haven’t seen a clinical trial of this comparison so I think it would be a great point to study.
Multiomic analysis of gamma MSC-suppressed alloreactive T cells
Kyndal Goss, Emory University (Georgia, USA)
Tell us about your research
Absolutely. Loads of patients undergo allogeneic hematopoietic stem cell transplantation and a large proportion of them can develop graft-versus-host disease (GVHD). We do have some standard GVHD prophylaxis, but they’re not entirely effective and they come with all kinds of unwanted side effects. So, it’s crucial to find a GVHD prophylaxis that’s more efficient. So that’s where we come in with mesenchymal stromal cells, specifically when primed with interferon gamma – we call them gamma MSCs. They’ve been shown to suppress alloreactive T cells, which are the cells causing GVHD, and they’ve been shown to reduce GVHD severity in mice. However, an FDA-approved therapy hasn’t been developed because the actual mechanism of how they work is unknown. So, the goal of my project is to understand that mechanism. I specialize in bioinformatics and computational immunology so I’m utilizing single-cell multi-omics to help us answer that question.
Could you explain some of the methods that you use for this research
We took naive T cells from five anonymous human donors and activated them with allogeneic dendritic cells. In our control group, they were in fresh media for day 0-6. In our experimental group, they were exposed to gamma MSCs for 48 hours and then placed back into fresh media. We took samples each day and used them to create sequencing libraries for 10x multiom, which is a newer technology that allows us to do single cell RNA-Seq and single-nuclease ATAC-Seq from the same single cells. So that’s the kind of up-and-coming technology that we use.
And how are you using that data?
We’re using that sequencing data to build gene regulatory networks, which are just a combination of regulons, which is a transcription factor in its target genes. We’re going to look at those and see which ones are disrupted by gamma MSCs, and also whichever ones are disrupted, how soon do they recover once the gamma MSCs have waned. Or they may not recover. But based on our preliminary data, we think that they do, and they start looking like controls by the end of that period. We have a clinical trial coming up, with both children and adults, where we’re going to be treating them with the gamma MSCs.
If you had unlimited resources, what work would you do next?
There are some newer technologies like DOGMA-Seq where you are able to get the single cell gene expression, single cell chromatin accessibility, as well as the cell surface protein expression like CITE-Seq, but that’s not necessarily super available yet. Obviously, in projects like this, the more cells, the better. We have about 114,000 cells here, but as these technologies are improving and growing we could eventually get into millions and millions of cells.