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.
Highlights
Mucins are a family of glycoproteins that are known to play central roles in biology.[1,2] Transmembrane mucins mediate important cell−cell interactions, as well as signaling events with other biomolecules such as lectins.[3,4] Misregulation during mucin synthesis has been linked to inflammation and tumor development.[5]
Mucin-like tumor antigens have been developed for circulating cancer cells with the aim of triggering a humoral response and so inducing active immunity at a stage of disease progression for which there are few alternative therapies.[6−8] More recently, synthetic mucin mimics have been designed as microarrays[9] and mucin chimeras have been assembled on living cells[10] to examine the complex biological roles played by cell surface mucins
PGMA55-PHPMA135 worm gels were synthesized at 20% w/v solids in Phosphatebuffered saline (PBS) followed by dialysis at 4 °C for 2 days against PBS, and diluted to produce a 6% w/v worm gel with cell culture medium
Summary
Mucins are a family of glycoproteins that are known to play central roles in biology.[1,2] Transmembrane mucins mediate important cell−cell interactions, as well as signaling events with other biomolecules such as lectins.[3,4] Misregulation during mucin synthesis has been linked to inflammation and tumor development.[5]. These observations suggest that synthetic mucin mimics may be promising active biomaterials for regenerative medicine
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