A bone marrow mimicry bioreactor for cost effective production of hematopoietic stem cells

Ziel

Hematopoietic stem/progenitor cell (HSPC) therapies have the potential to treat over 70 diseases including blood cancers and leukemia and are one of only 22 advanced therapy medicinal products currently approved by the European Medicines Agency. However, the number of HSPCs derived from a single blood donation can be insufficient for modern therapies, which typically require a minimum of 10^7 cells. To service adequate treatment regimes, HSPCs must be expanded in the laboratory at great financial expense, resulting in exorbitant treatment costs of up to 315,000. New methods of ex vivo HSPC expansion are therefore required to reduce production costs and ensure therapy affordability.
The industry standard for HSPC expansion utilises liquid suspension bioreactors, where cells are diluted in litres of culture media to a final concentration of only 10^3-5 cells/mL. This liquid media, containing large amounts of expensive nutrients, provides high cell expansion but results in high production costs. Liquid suspension bioreactors vary significantly from how humans grow HSPCs within high-cell-density tissue (10^8-11 cells/mL), which require only a fraction of the nutrient quantities per-cell.
The bone marrow is the human bodys natural HSPC bioreactor and provides a defined microenvironment for optimal cell production. I aim to artificially replicate these niche conditions by creating a marrow mimicry bioreactor (MarrowMimi) to maximise ex vivo HSPC expansion by (1) formulating a hydrogel scaffold to mimic the bone marrow extracellular matrix, (2) utilising state-of-the-art 3D printing technologies to create a marrow-like perfusion bioreactor, and (3) optimising reaction conditions to maximise HSPC expansion and minimise nutrient demand. The ability to minimise HSPC expansion-associated costs could ensure lifesaving therapies are more widely available to the community, therefore, MarrowMimi will focus on optimising methods for cost effective ex vivo HSPC production.