Utilizing polyHIPE scaffolds for the culture and analysis of human peripheral blood hematopoietic stem and progenitor cell expansion and proliferation.Blood cells are produced in the unique surroundings of the bone marrow from stem cells, which differentiate with the right mix of cellular signals and space to grow. Mimicking these conditions is tricky – even the best artificial systems produce significantly fewer blood cells than natural bone marrow. Now researchers have developed a highly porous polymer foam that resembles the bone marrow environment more closely [Severn et al., Biomaterials 225 (2019) 119533, https://doi.org/10.1016/j.biomaterials.2019.119533].
“We used a three-dimensional sponge scaffold to mimic bone marrow,” says first author of the study, Charlotte E. Severn. “We were able to maintain our hematopoietic stem cell (HSC) input for longer than a traditional two-dimensional liquid culture, with the ultimate goal of increasing the yield of cultured red blood cells.”
In conventional liquid culture processes, stem cells are used up very quickly as they differentiate. Large volumes of culture media laced with cytokines and growth factors are also needed. Using the three-dimensional culture developed by Ash M. Toye at the University of Bristol, along with collaborators at the National Research Centre in Egypt, the University of Warwick, University of Amsterdam, and Monash University, with funding from the National Institute of Health research, cuts the amount of culture media and expensive additives needed for the stem cell proliferation stage.
“Our polystyrene-based scaffold is made using a technique called emulsion templating, where an emulsion phase is formed over an aqueous phase,” explains Severn.
The highly porous foam, known as a polymerized high internal phase emulsion (polyHIPE), resembles a honeycomb. This compartmentalized structure supports the proliferation and growth of blood-forming stem cells, while retaining the initial population of cells over a long period. Cells produced within the material can be removed or allowed to return to the scaffold to repopulate it. This capability has not been reported previously, say the researchers, and could be unique to polyHIPE scaffolds.
“We have demonstrated, in effect, a self-selecting scaffold,” says Severn. “The scaffold could be used for the culture of cells in suspension, such as HSCs, neutrophils, or erythroid cells. It could also find application for HSC expansion in stem cell transplantation.”
Free thiol groups on the surface of the foam make functionalization with other biomolecules to boost cell production easy. Ultimately, the system could potentially be used as a bone marrow model for drug testing or to prolong the culture of rare patient samples.
“We are now working to identify proteins for a new generation of scaffolds designed to provide additional signals to drive stem cell proliferation even further,” says Toye. “This could enable us produce transfusion components or help researchers explore blood production in healthy and diseased systems in the lab.”