Stem cells/iPSCs, as well CRISPR/Cas9 are relatively new technologies and requires time to create technology for mass production with high efficacy and quality.
Stem-cell start-ups seek to crack the mass-production problem
Commercial outfits are building the tools and know-how to manufacture treatments using induced pluripotent stem cells in the quantities required for clinical use.
In the laboratory, induced pluripotent stem (iPS) cells can seem like magic: derived from differentiated cells, they can then morph into surprisingly good replacements for pancreatic, brain, eye, heart and other cells. Some are being used in clinical trials to treat people with chronic conditions, including diabetes and Parkinson’s disease, that are driven by damage to such cells (see page S8).
But it’s magic done slowly, for one patient at a time. “Essentially, all the cells are made by hand, by highly trained scientists sitting in a clean room,” says Nabiha Saklayen, a physicist and chief executive of Cellino Biotech in Cambridge, Massachusetts, a start-up developing a platform for manufacturing iPS cell therapies. “That’s not scalable.”
James Shapiro, a surgeon at the University of Alberta in Edmonton, Canada, concurs. Shapiro leads a team readying for a clinical study of pancreatic islet cells, created from iPS cells, that can take on the vital task of
producing insulin in people with type 1 diabetes. Testing such transplants in a handful of patients “will be exciting and will move the needle quite a bit”, he says.
“But it won’t address the big challenge ahead for personalized medicine: how on Earth could we ever do this kind of work for thousands of patients?” Shapiro says. “Right now it takes a technician and a crew of other research associates working day and night to baby these cells along to grow them into islet-like cells.”
To become practical therapies, stem-cell-based regenerative treatments must conquer two overlapping manufacturing challenges: achieving highly standardized automated production; and doing so in vastly greater volumes than at present.
To make an iPS-cell-based therapy, scientists first change the genes expressed by the starter cells to de-differentiate them into a pluripotent state. Gradual refinement of the techniques involved has made that relatively straightforward. But those pluripotent cells must then be differentiated at scale into the desired cell type — typically a much more formidable undertaking, says Jeffrey Millman, a bioengineer at Washington University in St. Louis, Missouri.
Biotech firms are responding to the challenge with an amazingly diverse range of technologies, says Bollenbach. Some companies are evolving production systems that were originally created to deliver other cell therapies, such as CAR-T cells used to treat blood cancers.
Other firms were launched to provide mass production and differentiation of iPS cells. In April, TreeFrog Therapeutics in Bordeaux, France, announced production of a single batch of 15 billion iPS cells in a week — an encouraging milestone. The company’s technology allows cells in the bioreactors to self-organize into aggregates similar to those formed by natural stem cells and protects them from shear stresses. TreeFrog is now working with several partners to build towards clinical trials for Parkinson’s disease and other conditions.
Commercial outfits are building the tools and know-how to manufacture treatments using induced pluripotent stem cells in the quantities required for clinical use.
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