Mucin-Inspired Thermoresponsive Synthetic Hydrogels Induce Stasis in Human Pluripotent Stem Cells and Human Embryos.
Mucin-Inspired Thermoresponsive Synthetic Hydrogels Induce Stasis in Human Pluripotent Stem Cells and Human Embryos.
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DOI：
10.1021/acscentsci.5b00370
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发表时间：
2016-02-24
影响因子：
18.2
通讯作者：
Armes SP
中科院分区：
文献类型：
--
作者：
Canton I;Warren NJ;Chahal A;Amps K;Wood A;Weightman R;Wang E;Moore H;Armes SP
人多能干细胞（hPSCs，包括胚胎和诱导多能干细胞）在贴壁培养中快速增殖以保持其未分化状态。然而，对于延迟妊娠（滞育）的哺乳动物，粘蛋白包裹的胚胎可以在子宫内保持休眠数天或数月，其组成的psc在这些条件下保持多能性。在这里，我们报道了hPSC菌落和着床前胚胎浸泡在由聚（单甲基丙烯酸甘油）-聚（2-羟丙基甲基丙烯酸酯）[PGMA55-PHPMA135]双嵌段共聚物蠕虫组成的全合成热响应凝胶中的细胞停滞。这种富含羟基的模拟黏液的非粘附3D凝胶在静止的G0状态下保持PSC的活力和多能性，无需传代至少14天。同样，涂有凝胶的人类胚胎也可以保持8天的假死状态（滞育）。人类造血干细胞和胚胎的隐细胞阻滞机制的发现表明，在引起胚胎滞育和多能性的细胞机制之间存在重要联系。此外，这种合成的蠕虫凝胶对于短期（数周）储存多能干细胞或人类胚胎没有冷冻保存提供了相当大的效用。完全合成的模拟黏液的羟基功能二嵌段共聚物自组装形成热响应性水凝胶，诱导人类多能干细胞和人类胚胎停滞。
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. Wholly synthetic mucin-mimicking hydroxyl-functional diblock copolymers self-assemble to form thermoresponsive aqueous hydrogels that induce stasis in human pluripotent stem cells and human embryos.