Synthetic bone marrow made from silk can grow platelets
Platelet transfusion is an essential procedure for patients who cannot produce enough of their own, often due to leukaemia, cancer treatment or viral disease. Yet the supply of donor platelets is unable to meet current demand, which is growing at around 10 % per year. One promising new avenue for boosting supply is ex vivo platelet production systems. As well as a scalable supply, growing platelets outside the body offers universal compatibility to avoid adverse immune reactions, and a reduced risk of cross-infection. The SilkPlatelet(opens in new window) project, funded through the European Innovation Council(opens in new window), developed a new ex vivo platelet production system based on silk fibroin, a natural protein fibre extracted from the cocoons of domesticated silkworms. The system employs a bioreactor to mimic the natural production from bone marrow, differentiating stem cells into precursors of megakaryocytes, the cells in bone marrow that produce platelets. The overall goal is to produce a solution for large-scale platelet production and transfusion. “The difference between our approach and others is that we didn’t adapt the technology to blood production, we did the opposite: we started with blood production, and then we developed the technology,” says Alessandra Balduini, professor in the Department of Molecular Medicine at the University of Pavia(opens in new window) in Italy and SilkPlatelet project coordinator. “It’s a unique approach.”
Improved silk-based bone marrow models
The system works by tricking lab-grown megakaryocytes into thinking they are inside a human body, convincing them to produce platelets on demand. It incorporates bone marrow engineered from silk fibroin, which closely mimics the sponge-like structure, composition and mechanics of real bone marrow. These silk-based bone marrow models can then produce platelets on a large scale. Through the SilkPlatelet project, the research consortium optimised the platelet production platform, improving the silk models to better mimic the human bone marrow environment and scale up the system to work towards large-scale production, working towards the EU4Health strategy(opens in new window) goal of increased access to life-saving treatments. Members of the consortium, led by Hana Raslova at the Institut Gustave Roussy(opens in new window) in Paris, France, also worked to improve platelet production yield, functionality and purity, optimising the platform to generate larger numbers of functional platelets. In parallel, all cell products underwent comprehensive quality control to ensure their identity, purity, functionality and safety before downstream applications. Ida Biunno and her team at ISENET Biobanking(opens in new window) in Italy further contributed by supporting the establishment, characterisation and quality assessment of the induced pluripotent stem cell lines used throughout the project, ensuring the robustness and reproducibility of the manufacturing process.
A flexible model to study disease
The proof of concept demonstrated that the ex vivo cells are not only functional, but flexible enough to act as though they were part of the human body – including replicating the impacts of platelet-related diseases, allowing the platform to be used to facilitate future research. “We were also able to replicate the complexity of the bone marrow with more cells, not only the progenitors, and show the impact of the different cells of the bone marrow on the production of blood,” explains Balduini. Balduini and her team are continuing to refine and improve the system, finding new applications and scaling up the bioreactor. “From the silk side, we are doing a lot: we are really trying to understand what silk is doing to the system and what we can improve,” adds Balduini.