The traditional compound for cryopreservation has for decades been dimethyl sulfoxide.

This organic solvent, even though well-known to most in the cryopreservation area, has a number of shortcomings.

See below:

Dyrkingshallen Square 2
  • Severe adverse reactions

    • Reports of severe adverse reactions, such as cardiac or respiratory arrest, neurotoxicity and epileptic seizures1
      • From the USP: DMSO is associated with risk of predictable dose-dependent gastrointestinal, cardiovascular, and neurologic toxicities that typically are ascribed to histamine release2 
  • Changes in the cellular epigenetic state

    • DMSO shown to induce hydroxymethylation (5hmC) and reduce methylation (5mC) in pre-osteoblastic MC3T3-E1 cells2
    • Increase expression and activity of de novo methyltransferase3
    • Directly cause methylation of cytosine4 
  • Strong and unpleasant smell

    • Strong and unpleasant smell which is a severe nuisance for staff, patients, and their surroundings 
      • From the USP: DMSO is categorized by ICH as a Class 3 (relatively low risk) solvent or excipient in pharmaceutical products, and amounts of up to 50 mg/day, or less, are considered acceptable without justification (see ICH Q3C) 2 Cryopreserved cellular products frequently contain 10–20 times this amount unless they are washed after thawing. 
      • Other side effects include nausea, vomiting, diarrhoea, dysgeusia, rash and abdominal pain7 

    • Requests from regulators for alternatives5
  1. Gao d. et al. Bone Marrow Transplant. 2014 Apr;49(4):469-76  
  2. From the USP 38 <1044> "Cryopreservation of cells" (p. 827)        
  3. Kung A.W.C et al. FEBS Lett. 2006 Jan 9;580(1):121-6
  4. Robertson K.D. et al. Bioorg Chem. 2004 Aug;32(4):234-43
  5. Kasai H. et al. Bioorg Med Chem Lett. 2010 Jan 1;20(1):260-5
  6. Cox M.A., et al. Cell Tiss Bank, 2012, 13(2):203-15
  7. Syme R. et al. Biology of Blood and Marrow TransplantationVolume 10, Issue 2, February 2004, Pages 135-141 

 Other relevant DMSO literature 

  • Verheijen M. et al “DMSO induces drastic changes in human cellular processes and epigenetic landscape in vitro”, SCIENTIFIC REPORTS, 15 March 2019 
  • Galvao J. et al “Unexpected low-dose toxicity of the universal solvent DMSO”, The FASEB Journal, Vol 28, March 2014 
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