Improved Cryopreservation of Human Induced Pluripotent Stem Cell (iPSC) and iPSC-derived Neurons Using Ice-Recrystallization Inhibitors

被引:4
作者
Alasmar, Salma [3 ]
Huang, Jez [1 ]
Chopra, Karishma [3 ]
Baumann, Ewa [1 ]
Aylsworth, Amy [1 ]
Hewitt, Melissa [1 ]
Sandhu, Jagdeep K. [1 ,2 ]
Tauskela, Joseph S. [1 ]
Ben, Robert N. [3 ,5 ]
Jezierski, Anna [1 ,2 ,4 ]
机构
[1] Natl Res Council Canada, Human Hlth Therapeut Res Ctr, Ottawa, ON, Canada
[2] Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada
[3] Univ Ottawa, Fac Sci, Dept Chem & Biomol Sci, Ottawa, ON, Canada
[4] Natl Res Council Canada, Human Hlth Therapeut Res Ctr, Bldg M-54,1200 Montreal Rd, Ottawa, ON K1A 0R6, Canada
[5] Univ Ottawa, Dept Chem & Biomol Sci, DIorio Hall,10 Marie Curie St, Ottawa, ON K1N 6N5, Canada
关键词
induced pluripotent stem cells; neurons; cryopreservation; ice recrystallization inhibitors; ice recrystallization; viability; MESENCHYMAL STROMAL CELLS; ROCK INHIBITOR; SPINAL-CORD; NEURAL STEM; DOPAMINE NEURONS; NEURITE OUTGROWTH; PROGENITOR CELLS; EFFICIENT; SURVIVAL; GROWTH;
D O I
10.1093/stmcls/sxad059
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Human induced pluripotent stem cells (iPSCs) and iPSC-derived neurons (iPSC-Ns) represent a differentiated modality toward developing novel cell-based therapies for regenerative medicine. However, the successful application of iPSC-Ns in cell-replacement therapies relies on effective cryopreservation. In this study, we investigated the role of ice recrystallization inhibitors (IRIs) as novel cryoprotectants for iPSCs and terminally differentiated iPSC-Ns. We found that one class of IRIs, N-aryl-D-aldonamides (specifically 2FA), increased iPSC post-thaw viability and recovery with no adverse effect on iPSC pluripotency. While 2FA supplementation did not significantly improve iPSC-N cell post-thaw viability, we observed that 2FA cryopreserved iPSC-Ns re-established robust neuronal network activity and synaptic function much earlier compared to CS10 cryopreserved controls. The 2FA cryopreserved iPSC-Ns retained expression of key neuronal specific and terminally differentiated markers and displayed functional electrophysiological and neuropharmacological responses following treatment with neuroactive agonists and antagonists. We demonstrate how optimizing cryopreservation media formulations with IRIs represents a promising strategy to improve functional cryopreservation of iPSCs and post-mitotic iPSC-Ns, the latter of which have been challenging to achieve. Developing IRI enabling technologies to support an effective cryopreservation and an efficiently managed cryo-chain is fundamental to support the delivery of successful iPSC-derived therapies to the clinic. Graphical Abstract
引用
收藏
页码:1006 / 1021
页数:16
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