Department of Mechanical Engineering, University of California at Berkeley, Berkeley, CA, 94720, USA.
Department of Bioengineering, University of California at Berkeley, Berkeley, CA, 94720, USA.
Commun Biol. 2021 Sep 22;4(1):1118. doi: 10.1038/s42003-021-02650-9.
Low-temperature biopreservation and 3D tissue engineering present two differing routes towards eventual on-demand access to transplantable biologics, but recent advances in both fields present critical new opportunities for crossover between them. In this work, we demonstrate sub-zero centigrade preservation and revival of autonomously beating three-dimensional human induced pluripotent stem cell (hiPSC)-derived cardiac microtissues via isochoric supercooling, without the use of chemical cryoprotectants. We show that these tissues can cease autonomous beating during preservation and resume it after warming, that the supercooling process does not affect sarcomere structural integrity, and that the tissues maintain responsiveness to drug exposure following revival. Our work suggests both that functional three dimensional (3D) engineered tissues may provide an excellent high-content, low-risk testbed to study complex tissue biopreservation in a genetically human context, and that isochoric supercooling may provide a robust method for preserving and reviving engineered tissues themselves.
低温生物保存和 3D 组织工程代表了两种不同的途径，可实现对可移植生物制剂的按需获取，但这两个领域的最新进展为它们之间的交叉提供了关键的新机会。在这项工作中，我们通过等容过冷展示了在亚零摄氏度下保存和复苏自主跳动的三维人诱导多能干细胞（hiPSC）衍生的心脏微组织，而无需使用化学冷冻保护剂。我们表明，这些组织在保存过程中可以停止自主跳动，并在升温后恢复跳动，过冷过程不会影响肌节结构完整性，并且组织在复苏后仍对药物暴露保持反应性。我们的工作表明，功能性三维（3D）工程组织可能为在遗传上人类背景下研究复杂组织生物保存提供一个极好的高内涵、低风险的试验台，并且等容过冷可能为保存和复苏工程组织本身提供一种强大的方法。
