Stem cells allow pharmaceutical companies to test new drugs more efficiently, and while thousands of stem cells are being collected and preserved in biobanks, the industry is still in need of pluripotent stem cells in large quantities.
Recently, scientists at the Fraunhofer Institute for Biomedical Engineering IBMT in Sulzbach have identified seaweed from Chile as an efficient source of nutrients for the expansion of pluripotent stem cells. Specifically, they have developed a production process for alginate, seaweed’s supporting structure.
The process involves everything from harvesting, to importing, and manufacturing. British pharmaceutical companies are currently validating the process in their laboratories.
The harvest
In a laboratory operated by IBMT and Fraunhofer Chile at UCN University in Coquimbo, the seaweed is individually peeled, shredded, and dried within 24 hours of harvest to prevent contamination. The resulting seaweed granulate is then exported to Germany where the alginate is extracted and shaped into beads using a strong jet of air.
“The beads are rendered more stable in a barium bath, as barium tends to remain in the seaweed mass,” explained Prof. Heiko Zimmermann, Managing Head of Fraunhofer IBMT. “The trick is to make the material stable, but not too hard.”
The protein-coated alginate is then placed into a bioreactor with the optimum temperature and C02 environment. Each alginate bead measures around 200 micrometers and performs the role of a Petri dish – allowing stems cells to propagate and grow over the alginate in three to seven days.
“Because the alginate volumes in the reactors can be increased slightly, we can grow pluripotent stem cells in greater quantities and in smaller spaces,” Zimmermann said.
The advantages
Alginate is suitable for stem cell cultivation as it consists of a highly aqueous gel more viscous than honey. When cross-linked with calcium or barium, alginate is stable, flexible, as well as permeable.
“Cells feel especially at home in elastic 3D environments such as are found inside the body. It’s precisely this environment that can be simulated perfectly using alginate,” Zimmermann explained.
Additionally, the scientists are able to change its elasticity by mixing seaweed species and producing the alginate in various bead sizes. “After all, different cells need different culture conditions,” he added.
The researchers introduced active ingredients into the alginate, such as those that transform pluripotent stem cells into somatic cells.
“In the future … the alginate will not only act as a passive substrate, but will also actively influence the growth of the stem cells,” said Zimmerman.
Another advantage of alginate is the absence of autofluorescence, which is important for optical analysis.
“The stem cells grow better on our alginate – and particularly well in automated bioreactors,” added Zimmerman. “They differentiate better into the desired somatic cells than on the plastic substrates generally used today.”
The first concrete trials with partners from the European Federation of Pharmaceutical Industries and Associations (EFPIA) are planned for next year. According to Zimmerman, the goal is to demonstrate that the process can produce stable pluripotent stem cells.
“At the institute, we’ve already managed to do just that for many individual stem cell lines."