Editors' ChoiceStem Cell Production

Improving Stem Cell Survival, One Hurdle at a Time

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Science Translational Medicine  29 Sep 2010:
Vol. 2, Issue 51, pp. 51ec149
DOI: 10.1126/scitranslmed.3001729

Use of stem cells as a therapeutic agent in the clinic is limited by the technical hurdles encountered during their production. Better laboratory culture is needed to improve their propagation and availability. Cell lines that can produce millions of self-renewing pluripotent cells from a single embryonic stem cell are hard to generate because they tend to fare poorly at the required single-cell (clonal) density. Walker et al. have now demonstrated that inhibition of nonmuscle myosin II (NMII) improves survival and supports renewal of human embryonic stem cells (hES cells) and human induced pluripotent stem cells (hiPS cells).

Building on a previous study in which these authors showed that NMII is important for cell-cell junctional assemblies of hES cells, the researchers cultured single hiPS cells in the presence of a specific chemical inhibitor of NMII called blebbistatin. These cells showed an increase in survival and colony formation as well as enhanced expression of pluripotency markers. Mouse embryonic stem cells behaved similarly when the NMII gene was mutated or inhibitory short hairpin–mediated RNA to NMII was expressed, with improved survival and expression of self-renewal regulators such as Oct4 and Nanog. This mechanistic link was further supported by the induction of self-renewal regulators under NMII inhibition with and without specialized media supporting differentiation. On the basis of these findings, the authors prepared culture medium for hES or hiPS that contained the NMII inhibitor and that better supported cell survival and self-renewal for extended period of time. Even more interesting, these cells maintained their genomic integrity and ability to differentiate into multiple tissues derived from all three germ layers when they were injected into severe combined immunodeficient (SCID) mice.

These studies indicate that NMII inhibition may improve hES cell survival enough to enable large-scale production of stem cell lines for drug screening and cell transplantation. This will further the fulfillment of the promise of stem cell therapy for patients suffering from debilitating diseases.

A. Walker et al., Non-muscle myosin II regulates survival threshold of pluripotent stem cells. Nat. Commun. 1 September 2010 (10.1038/ncomms1074). [Abstract]

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