title: Mucin-Inspired Thermoresponsive Synthetic Hydrogels Induce Stasis in Human Pluripotent Stem Cells and Human Embryos.
abstract: Human pluripotent stem cells (hPSCs; both embryonic and induced pluripotent) rapidly proliferate in adherent culture to maintain their undifferentiated state. However, for mammals exhibiting delayed gestation (diapause), mucin-coated embryos can remain dormant for days or months in utero, with their constituent PSCs remaining pluripotent under these conditions. Here we report cellular stasis for both hPSC colonies and preimplantation embryos immersed in a wholly synthetic thermoresponsive gel comprising poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) [PGMA55-PHPMA135] diblock copolymer worms. This hydroxyl-rich mucin-mimicking nonadherent 3D gel maintained PSC viability and pluripotency in the quiescent G0 state without passaging for at least 14 days. Similarly, gel-coated human embryos remain in a state of suspended animation (diapause) for up to 8 days. The discovery of a cryptic cell arrest mechanism for both hPSCs and embryos suggests an important connection between the cellular mechanisms that evoke embryonic diapause and pluripotency. Moreover, such synthetic worm gels offer considerable utility for the short-term (weeks) storage of either pluripotent stem cells or human embryos without cryopreservation.
authors.affiliation: Department of Biomedical Science, University of Sheffield , Sheffield, S10 2TN, U.K.
authors.forename: Irene
authors.initials: I
authors.lastname: Canton
authors.affiliation: Department of Chemistry, Dainton Building, University of Sheffield , Sheffield, S3 7HF, U.K.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Warren
authors.affiliation: Department of Biomedical Science, University of Sheffield , Sheffield, S10 2TN, U.K.
authors.forename: Aman
authors.initials: A
authors.lastname: Chahal
authors.affiliation: Department of Biomedical Science, University of Sheffield , Sheffield, S10 2TN, U.K.
authors.forename: Katherine
authors.initials: K
authors.lastname: Amps
authors.affiliation: Department of Biomedical Science, University of Sheffield , Sheffield, S10 2TN, U.K.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wood
authors.affiliation: Department of Biomedical Science, University of Sheffield , Sheffield, S10 2TN, U.K.
authors.forename: Richard
authors.initials: R
authors.lastname: Weightman
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Louisville , Louisville, Kentucky 40202, United States.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Wang
authors.affiliation: Department of Biomedical Science, University of Sheffield , Sheffield, S10 2TN, U.K.
authors.forename: Harry
authors.initials: H
authors.lastname: Moore
authors.affiliation: Department of Chemistry, Dainton Building, University of Sheffield , Sheffield, S3 7HF, U.K.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Armes