>This is very cool research that can impact so many lives! Thanks for the work that you do.
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>My question is: Is it possible to also differentiate stem cells to other types of blood cells like platelets and white blood cells?

Hello, thank you for the great question! The starting cell type, known as BEL-A cells (developed by scientists at University of Bristol) that we work with, have been succesfully matured into red blood cells that are similar to native red blood cells found in the body - their biological signature and performance (e.g. oxygen-binding capacity) are comparable. Our aim of designing 'bioreactors' to mass manufacture these cells will be followed up with a list of criteria that we will check against to make sure that our bioreactor-produced cells are comparable to native red blood cells.

Thanks for you question! I (Sandhya) am a biotechnologist (so expert in bioreactors) and stem cell engineer. I (David) very much have a background in biology – I did my undergrad in Applied Biology and a Masters in Stem Cells and Regeneration. I chose this project because I was keen to work with stem cells and bioreactors, and because I wanted to contribute to a project that could make a real different to people’s lives and wellbeing. I (Chan) am a (bio)chemical engineer (Chan) and although I had taken a few biochemical modules on how to produce biomass, cells, and proteins in a bioreactor, I had to learn the cell biology of RBCs and the biological process behind it. I have chosen this project because as a biochemical engineer, I enjoy optimisation and the production process, but I always enjoyed medical science, which triggered my interest in this project.

Thank you so much for your kind words and the great question! If we use the right starting cell type, we can theoretically produce any target cell type of interest. For instance, we use red blood progenitor cells, which are what we refer to as 'lineage-committed' - so they can only mature into red blood cells and not other cell types in the blood tissue. However, the technology we are developing could use any starting cell type from the blood tissue - so if we were to use haematopoietic stem cells (not lineage-committed), we could potentially produce other cell types in the blood tissue such as white blood cells and platelets.

Thank you for your question! Bioreactor technologies are being developed for a variety of cell types and this is an area of active research. There are many challenges with growing any cell type outside the body including red blood cells (RBCs). We aim to manufacture RBCs to address the growing shortage of donated blood globally. Within the different cell types in blood, we are focussed on RBCs since they are the oxygen-carying component of blood and hence, if we can replenish them for a patient who has suffered major blood loss, we can save the patient's life and their body is then able to replenish the other cell types in the blood tissue.

We can manufacture RBCs using existing bioreactor technologies, but these technologies are not yet fully optimized for cost-effective manufacture. Our research focuses on optimizing these technologies (that were developed for other cell types) specifically for cost-effect mass RBC manufacture. Current cost of donated blood is ~£125/unit (it is >£500/unit for rarer blood types) while that for bioreactor-produced RBCs is >£5,000/unit. Our research aims to design better bioreactors to bring down costs closer to that of donated blood.

Thank you for the great question! It would definitely be cool to make extra efficient red blood cells that work way better than the naturally occuring ones! It would be a whole new area of research for blood biologists. However, as engineers, we are currently working with the cells that the biologists have developed and given to us, so the naturally occuring red blood progenitor cells and we are aiming to grow and mature them in red blood cells that would deform in the same manner (essential to allow them to navigate through blood vessels) and they bind and release oxygen in the same manner to naturally occuring ones in our bodies.

Thank you for the question, if blood transfusion is the current mode of treatment, then yes our researach will definitely be of help. In addition, for people requiring regular transfusions, the cells we manufacture would theoretically be better in terms of blood type matching and risk of immune rejected (also known as alloimmunization)

 Great question, thank you! It is both cutting edge and doable, however, currently it is expensive to mass produce them to be used in the clinic for blood transfusions. We can make a few millilitres in the lab, but existing technology does not support making 'units' of blood in a cost-effective manner (compared to donated blood costs). So you're correct - one of our key research aims is to design a 'bioreactor' technology that will make the red blood cell manufacturing process more efficient and hence cost-effective.

Yes, absolutely! It is the key aim of using technologies such as the bioreactor. We start with a small number of stem cells or progenitor that have the capacity to divide and give rise to more stem/progenitor cells, under the right conditions. Once we get enough starting stem/progenitor cells, we then modify the bioreactor conditions to promote their maturation (also known as differentiation) to form red blood cells. Our research aims to identify these best conditions to grow and mature these cells within bioreactors, as well as the starting cell number and final cell numbers we can get from the bioreactor.

Thanks for the question! We currently work with red blood progenitor cells that will give rise to the universal blood type RBCs.

The typical shelf life for donated RBCs is up to 42 days. We are currently working on answering this question, but we would expect it to have a longer shelf life as it a pure population of young and pure population of red blood cells.

We’ve contacted Fangtasia as a potential business partner :)