4.7 Article

Synthetically Scalable Poly(ampholyte) Which Dramatically Enhances Cellular Cryopreservation

期刊

BIOMACROMOLECULES
卷 20, 期 8, 页码 3104-3114

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.9b00681

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资金

  1. ERC [638661, 789182]
  2. EPSRC Centre for Doctoral Training in Molecular Analytical Science [EP/L015307/1RT]
  3. Wellcome Warwick Quantitative Biomedicine Programme (Institutional Strategic Support Fund) [105627/Z/14/Z]
  4. Wellcome Trust-Warwick QBP program
  5. BBSRC ALERT14 Award [BB/M01228X/1]
  6. European Research Council (ERC) [789182] Funding Source: European Research Council (ERC)
  7. Wellcome Trust [105627/Z/14/Z] Funding Source: Wellcome Trust
  8. BBSRC [BB/M01228X/1] Funding Source: UKRI

向作者/读者索取更多资源

The storage and transport of frozen cells underpin the emerging/existing cell-based therapies and are used in every biomedical research lab globally. The current gold-standard cryoprotectant dimethyl sulfoxide (DMSO) does not give quantitative cell recovery in suspension or in two-dimensional (2D) or three-dimensional (3D) cell models, and the solvent and cell debris must be removed prior to application/transfusion. There is a real need to improve this 50-year-old method to underpin emerging regenerative and cell-based therapies. Here, we introduce a potent and synthetically scalable polymeric cryopreservation enhancer which is easily obtained in a single step from a low cost and biocompatible precursor, poly(methyl vinyl ether-alt-maleic anhydride). This poly(ampholyte) enables post-thaw recoveries of up to 88% for a 2D cell monolayer model compared to just 24% using conventional DMSO cryopreservation. The poly(ampholyte) also enables reduction of [DMSO] from 10 wt % to just 2.5 wt % in suspension cryopreservation, which can reduce the negative side effects and speed up post-thaw processing. After thawing, the cells have reduced membrane damage and faster growth rates compared to those without the polymer. The polymer appears to function by a unique extracellular mechanism by stabilization of the cell membrane, rather than by modulation of ice formation and growth. This new macromolecular cryoprotectant will find applications across basic and translational biomedical science and may improve the cold chain for cell-based therapies.

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