title: Natural zwitterionic betaine enables cells to survive ultrarapid cryopreservation.
abstract: Cryoprotectants (CPAs) play a critical role in cryopreservation because they can resist the cell damage caused by the freezing process. Current state-of-the-art CPAs are mainly based on an organic solvent dimethyl sulfoxide (DMSO), and several DMSO-cryopreserved cell products have been brought to market. However, the intrinsic toxicity and complex freezing protocol of DMSO still remain as the bottleneck of the wide use for clinical applications. Herein, we reported that betaine, a natural zwitterionic molecule, could serve as a nontoxic and high efficient CPA. At optimum concentration of betaine, different cell types exhibited exceptional post-thaw survival efficiency with ultrarapid freezing protocol, which was straightforward, cost efficient but difficult to succeed using DMSO. Moreover, betaine showed negligible cytotoxicity even after long-term exposure of cells. Mechanistically, we hypothesized that betaine could be ultra-rapidly taken up by cells for intracellular protection during the freezing process. This technology unlocks the possibility of alternating the traditional toxic CPAs and is applicable to a variety of clinical applications.
authors.affiliation: Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China.|Key Laboratory of Systems Bioengineering of the Ministry of Education, Tianjin University, Tianjin 300072, P. R. China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, 300072, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China.|Key Laboratory of Systems Bioengineering of the Ministry of Education, Tianjin University, Tianjin 300072, P. R. China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, 300072, P. R. China.
authors.forename: Nana
authors.initials: N
authors.lastname: Cai
authors.affiliation: Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China.|Key Laboratory of Systems Bioengineering of the Ministry of Education, Tianjin University, Tianjin 300072, P. R. China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, 300072, P. R. China.
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhai
authors.affiliation: Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China.|Key Laboratory of Systems Bioengineering of the Ministry of Education, Tianjin University, Tianjin 300072, P. R. China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, 300072, P. R. China.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China.|Key Laboratory of Systems Bioengineering of the Ministry of Education, Tianjin University, Tianjin 300072, P. R. China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, 300072, P. R. China.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China.|Key Laboratory of Systems Bioengineering of the Ministry of Education, Tianjin University, Tianjin 300072, P. R. China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, 300072, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D001622:Betaine / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015925:Cryopreservation; D019610:Cytoprotection / Q000187:drug effects; D005615:Freezing; D006367:HeLa Cells; D006801:Humans; D007053:Ice; D009997:Osmotic Pressure
chemical_list: D007053:Ice; D001622:Betaine