Transplanted stem cells have been used as regenerative therapies for decades. In cancer, for example, they can restore the body’s ability to create the red blood cells, white blood cells, and platelets after chemotherapy.
But stem cells have wider therapeutic potential. In theory they can be reprogrammed to regenerate tissues damaged in diseases ranging including type 1 diabetes, Parkinson’s, amyotrophic lateral sclerosis, and Alzheimer’s.
Despite this potential, to date only one stem cell therapy—the ocular burns treatment Holoclar—has been approved by a major regulator.
Manufacture is a major challenge that holds back the sector, according to Steve Oh, director of stem cell bioprocessing at Singapore’s Agency for Science, Technology and Research (A*STAR).
“There are a range of process manufacturing challenges,” he says, citing the development of robust and reproducible production processes, maintaining the “stem-ness” of the cells through multiple passaging steps and cryopreservation as examples.
To try and address the scalability issue Oh and colleagues developed a micro-carrier-based culturing process—in which the cells grow on the surface of beads in solution—to increase productivity.
“Part of the idea is to increase surface area of growth,” he says, adding “Volumetric productivity is increased with growing bioreactor scales from 1, 5, 10, 50 liters and so forth with a small area footprint.”
In addition, Oh notes, protein coatings such as laminin, vitronectin, and fibronectin can be added to the surfaces of the carriers to cater to different cell types.
The approach also reduces manual steps, continues Oh, who reports that “integrated expansion followed by differentiation can be performed in the same bioreactor with automation instead of manual handling over long culture times.”
“In addition, higher densities can be achieved than monolayers; all these benefits reduce the overall costs of goods for biomanufacturing.”
The A*STAR technology was recently licensed to Singapore-based contract development and manufacturing organization (CDMO) SingCell, which is offering it as a service to cell therapy companies.
Innovative bioprocessing technologies and methods will also be needed to address other challenges that stem cell developers face, observes Oh.
“We are at the early stage of stem cell biomanufacturing development and there will be a need for continuous process development. For example, integrating of gene delivery at scale for genetically engineered lines and efficient harvesting technology are two areas that require development,” he says.
“We are also applying machine learning to predict the qualities of stem cells than can give the best therapeutic outcomes for diseases like osteoarthritis and going back to the bioprocess to give these qualities to the cells.”