Researchers Present Novel Method for Scale-Up of Stem Cell Production

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This new method uses inter-alpha inhibitors to promote attachment and long-term growth in stem cells.

A group of researchers from the the University of Nottingham, Uppsala University, and GE Healthcare have developed a novel method for scale-up of human stem cells, according to a new study published in Nature Communications. This new research, published on July 13, 2016, could potentially provide a viable method for large-scale production of stem cells.

The study authors use inter-alpha inhibitors (IαI), a human serum-derived protein, to promote attachment and long-term growth in embryonic and human pluripotent stem cells (hPS) by adding it to the medium at seeding. Researchers present a “completely defined xeno-free medium that supports long-term propagation of hPS cells on uncoated tissue culture plastic…[consisting] of the Essential 8 (E8) formulation supplemented with IαI.” The use of IαI gives hPS the ability to survive in the absence of Rho-associated kinase inhibitor, researchers say.

“This new method removes the need for a pre-treated surface, and shows better survival in harsh conditions,” Sara Pijuan Galitó, PhD, study author and postdoctoral researcher at Uppsala University, told BioPharm International. “Therefore it will have great implications for future large-scale and automated expansion of human pluripotent stem cells.”

However, it is important to note scale-up on a very large scale does lead to high instances of cell senescence, an issue scientists looking to scale-up stem-cell production will have to address. “In bioreactor-based large-scale expansion, due to larger volumes and required stirring for nutrient and oxygen exchange, higher cell death and lower proliferation has been reported. This is due harsher conditions in culture, and both cell death programs and senescence have been reported,” Galitó told BioPharm International.


Researchers also note the methods currently available for scale-up of stem cells are either too costly or lack reproducibility. Some researchers suggest scale-out as a more viable option for large scale production. According to Galitó although scale-out of cell development facilitates tighter quality controls, scale-up is more efficient and cost-effective.

“Bioreactor-based expansion has traditionally been preferred for its cost-effectiveness and large volume. Of course, in stem cell production cell quality is a key issue, and scale-out would facilitate tighter cell quality controls,” says Galitó. “Early clinical trials point to millions or even billions of cells required per patient and per treatment to achieve a beneficial effect. Therefore, I would say that it will result more cost and time- efficient to scale-up rather than scale-out the current, very small-scale methods validated for clinical-grade cell production.”

Source: Nature Communications