Editors' ChoiceStem Cells

Room for Expansion

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Science Translational Medicine  14 Dec 2011:
Vol. 3, Issue 113, pp. 113ec202
DOI: 10.1126/scitranslmed.3003564

As the saying goes, “You get out what you put in.” Typically, this refers to matters of life and love. But it may apply equally well to a new bioprocess design strategy described by Ungrin et al. in their latest study. These researchers report how to fine-tune the differentiation of human pluripotent stem cells (hPSCs) into endodermal stem cells so that you can actually get out more than what you put in.

For some therapeutic applications, such as transplantation, billions of hPSCs are needed for each treatment, for each patient. To produce such vast numbers in the laboratory is a daunting task. Undeterred, Ungrin and colleagues tackled this problem by devising a bioprocessing strategy that optimizes various features of hPSC expansion and differentiation. First, they put hPSCs into suspension (as opposed to the usual adherent) culture in individual microsized wells and allowed aggregates to form. Then, the researchers looked at the dynamics of these stem cell aggregates, such as growth, survival, and differentiation, and found that tweaking external cues (instruction)—rather than the identity of the cell population (selection)—determined the efficiency of differentiation of hPSCs into endodermal progenitor cells. Next, Ungrin et al. confirmed that their endodermal progenitor cells (so-called definitive endoderm) were able to undergo subsequent stages of differentiation to form mature endodermal cells of pancreatic and hepatic lineages. Their strategy resulted in an output of 18 endodermal progenitor cells for each hPSC put into their culture system.

This scale-up method produces more endodermal progenitor cells with greater efficiency than do other techniques and preserves the cells’ ability to form pancreatic and liver cells—important advances if these cells are to be used therapeutically. The eventual goal is to generate enough endodermal cells for transplantation to treat human diseases such as type 1 diabetes or liver cirrhosis, a goal that may be one step closer thanks to this elegant study.

M. D. Ungrin et al., Rational bioprocess design for human pluripotent stem cell expansion and endoderm differentiation based on cellular dynamics. Biotechnol. Bioeng. 2 December 2011(10.1002/bit.24375). [Abstract]

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