The new approach – which was developed by researchers in Sweden and Singapore - involves growing a harvested embryonic stem cell into a culture on a matrix of two adhesion proteins: a recombinant of laminin-521 that is associated with pluripotent stem cells; and epithelial cadherin (E-cadherin).
As a result, it is now possible to take a single hES cell and culture it in vitro thereby providing sufficient material for a wide range of applications.
This is particularly significant for genetic analyses because, while using single hES has been possible, ensuring that sufficient DNA is available has more commonly involved taking a number of cells and effectively destroying the embryo as lead researcher Karl Tryggvason told BioPharma-reporter.com.
“It has been shown before that it is possible to take a so called single cell biopsy from an 8 or 16 cell IVF embryo for making DNA diagnosis in cases where there is a known genetic disease in the family.
“However, the DNA is not always sufficient for analysis in such cases. Now when it is possible to culture such a single cell in a culture dish, one actually gets enough DNA for genetic diagnosis and a stem cell line for the corresponding embryo.”
Another key aspect of the new hES growth matix is its human origin, which is particularly important for the production of cell therapies. At present most commercial growth matrix technologies are based on either animal cells or fibroblast cells harvested from human hosts, both of which can contaminate stem cells.
Tryggvason, who is professor of medical Chemistry at Karolinska Institutet and professor at Duke-NUS Graduate Medical School in Singapore, acknowledged this and stressed the animal-free nature of his own team’s technique as another advantage.
“It is important to be able to make hES cells for cell therapy use such that the cell line establishment system is chemically defined and does not contain animal proteins, or infectious agents. To have such a system is considered important from regulatory authorities’ point of view.”
“In our laminin system, every component is known, the cells grow as a monolayer of fully pluripotent cells each of which can be monitored for properties.”
Regulatory issues have certainly stymied the development of stem cell-based therapies in the past. In 2011, for example, Geron discontinued all of its clinical-stage programmes citing “regulatory complexities” as one of a number of factors that scuppered the project.
Big biopharma interest
Tryggvason is confident the technique has commercial application. He told us that: “Currently the main hurdles for making hES cells for research and cell therapy purposes have been ethical and technical. We have with the technique moved all those hurdles out of the way.”
“Several Big Pharmas are using our laminin-521 in their R&D nowadays. They are customers of the Stockholm-based biotech company BioLamina that was founded due to large number of requests that I got for recombinant laminins.”