Dr. Robert Zweigerdt from Hannover Medical School was the moderator and welcomed the group. Dr. Zweigerdt's work in reprogramming and the growth of human induced Pluripotent Stem Cells (hiPSCs) is quite impressive and has truly arrived at the forefront of stem cell bioprocessing. While the field is still young, Dr. Zweigerdt's group has shown tremendous progress using small-scale bioprocessing and parallel control to expand hiPSC populations without impacting their ability to retain stem cell identity and differentiate. In particular, the method to expand and differentiate hiPSCs into functional cardiomyocytes was particularly impressive and is a major focus of the field recently. Presenting these data along with another project aimed at expanding mesendoderm primitive streak cells as a novel model system was Dr. Henning Kempf. Discussions on the challenges involved in developing chemically-defined, animal/serum-free processes highlighted the rise in available media for this purpose - but the onus is on the research groups to determine which of these is sustainable and cost-effective for larger-scale production.
In addition to the other excellent talks of the morning, keynote speaker Dr. Steven Oh offered his expertise in the field of quality control in stem cell bioprocessing. As is well-known to stem cell biologists, one of the biggest challenges in stem cell expansion, aside from the expansion itself, is developing reproducible and robust assays to monitor the quality of the population at all stages of the process. Although flow cytometry assays exist for stem cell identity, and differentiation assays can determine whether or not the cells are still multipotent, both of these activities are far from high-throughput. The ideal would be a platform that could automatically assay for identity, differentiation, and senescence in a more automated and time efficient way. Also in this talk, Dr. Oh described the development of a biodegradable microcarrier which would uniquely allow for implantation of a stem cell therapy while it is still attached to the microcarrier without the problem of a plastic or glass microcarrier being co-implanted.
During the lunch break many researchers from around the globe presented posters. The open format allowed presenters to get to know one another and discuss their work openly.
The afternoon sessions brought more lively discussion on the challenges of working with these sensitive cell types, including a talk from Ricardo Baptista at Cell and Gene Therapy Catapult in the United Kingdom. The field has generally adopted a protocol involving fresh media feeding on a relatively frequent basis as compared to other mammalian cell lines. At Cell and Gene Therapy Catapult, they are working on using mass spectrometry to determine exactly what components of the medium are necessary in the feed medium - data which could streamline the stem cell bioprocessing workflow considerable by allowing less frequent or more optimized feeds. In addition, the group prefers a "Scale-out" approach to stem cell bioprocessing which was quite interesting. Instead of the conventional "Scale-up" technique where processes are developed in sequentially larger volumes to generate more biomass, the Scale-out technique relies on many small bioreactors, eliminating the risk and loss associated with the failure of a larger bioreactor. Although there has been much discussion in the field on scaling up between the micro-scale 15 mL bioreactors and the mini-scale 300 mL bioreactors, this group has had success using classic scale-up techniques.
Another excellent contribution was made by Lior Raviv, Vice President for Development from Pluristem. This company has a long history with packed-bed bioreactors and has applied this expertise and technology to stem cell bioprocessing with great success. Among other topics, one more major challenge in stem cell bioprocessing was discussed: batch-to-batch variation. Pluristem sees far less batch-to-batch variation in cell quality and health using a packed-bed system. Other advantages of this well-established technology include the ability to easily perfuse the culture, extremely low shear environment, and cGMP-compliance. In fact, this group has used bioreactor-derived biomass in a Phase 1 clinical trial. Questions generated a discussion on harvesting methods which included mechanical forces and enzymatic treatment – both of which were fully automated. The feeling was that this was a well-developed technique which generated very high cell densities.
Over all, the day truly lived up to the initial expectations and the feeling at the cocktail hour following the end of the talks was a pleasure. Discussions on topics ranging from stem cell basic research to bioprocessing were heard all over the room.
The Stem Cell Community Day 2019 will take place November 21 in Lisbon, Portugal. Find more information on www.stemcellday.de