Skip to main content

Advertisement

Log in

Determination of residual dimethylsulfoxide in cryopreserved cardiovascular allografts

  • Published:
Cell and Tissue Banking Aims and scope Submit manuscript

Abstract

Dimethylsulfoxide (DMSO) is a solvent which protects the structure of allografts during the cryopreservation and thawing process. However, several toxic effects of DMSO in patients after transplantation of cryopreserved allografts have been described. The aim of this study is to determine the residual DMSO in the cardiovascular allografts after thawing and preparation of cryopreserved allografts for clinical application following guidelines of the European Pharmacopoeia for DMSO detection. Four types of EHB allografts (aortic valve-AV, pulmonary valve-PV, descending thoracic aorta-DA, and femoral artery-FA) are cryopreserved using as cryoprotecting solution a 10% of DMSO in medium 199. Sampling is carried out after thawing, after DMSO dilution and after delay of 30 min from final dilution (estimated delay until allograft implantation). After progressive thawing in sterile water bath at 37–42 °C (duration of about 20 min), DMSO dilution is carried out by adding consecutively 33, 66 and 200 mL of saline. Finally, tissues are transferred into 200 mL of a new physiologic solution. Allograft samples are analysed for determination of the residual DSMO concentration using a validated Gas Chromatography analysis. Femoral arteries showed the most important DMSO reduction after the estimated delay: 92.97% of decrease in the cryoprotectant final amount while a final reduction of 72.30, 72.04 and 76.29% in DMSO content for AV, PV and DA, was found, respectively. The residual DMSO in the allografts at the moment of implantation represents a final dose of 1.95, 1.06, 1.74 and 0.26 mg kg−1 in AV, PV, DA and FA, respectively, for men, and 2.43, 1.33, 2.17 and 0.33 mg kg−1 for same tissues for women (average weight of 75 kg in men, and 60 kg in women). These results are seriously below the maximum recommended dose of 1 g DMSO kg−1 (Regan et al. in Transfusion 50:2670–2675, 2010) of weight of the patient guaranteeing the safety and quality of allografts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • David N (1972) The parmacology of dimethyl sulfoxide 6544. Annu Rev Parmacol 12:353–374

    Article  CAS  Google Scholar 

  • European Pharmacopoeia 5.0, 01/2005:0763

  • European Pharmacopoeia 7.0, 01/2008:50400

  • Gatto C, Dainese L, Buzzi M, Terzi A, Guarino A, Pagliaro PP, Polvani G, Tothova JD (2013) Establishing a procedure for dimethylsulfoxide removal from cardiovascular allografts: a quantitative study. Cell Tissue Bank. doi:10.1007/s10561-012-9331-3

    Google Scholar 

  • Hanslick JL, Lau K, Noguchi KK, Olney JW, Zorumski ChF, Mennerick S, Farber NB (2009) Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system. Neurobiol Dis 34:1–10

    Article  CAS  PubMed  Google Scholar 

  • ICH Q3C (R4): Guideline for residual solvents

  • Jashari R, Goffin Y, Van Hoeck B, Vanderkelen A, du Verger A, Fan Y, Holovska V, Fagu A, Brahy O (2010) Belgian and European experience with the European Homograft Bank (EHB) cryopreserved allograft valves.–assessment of a 20 year activity. Acta Chir Belg 110(3):280–290

    Article  CAS  PubMed  Google Scholar 

  • Jashari R, Van Hoeck B, Ngakam R, Goffin Y, Fan Y (2013) Banking of cryopreserved arterial allografts in Europe: 20 years of operation in the European Homograft Bank (EHB) in Brussels. Cell Tissue Bank 14(4):589–599. doi:10.1007/s10561-012-9359-4 Epub 2013 Jan 11

    Article  CAS  PubMed  Google Scholar 

  • Khawandanah M, Hopps S, Nabeel S, Ahmad B, Weiss S, Charkrabarty JH, Yuen C, Selby G (2014) DMSO induced myocardial infarction during allogeneic cryopreserved bone marrow transplant. Annu Hematol. doi:10.1007/s00277-014-2181-2

    Google Scholar 

  • Morley P, Whitfield JF (1993) The differentiation inducer, dimethyl sulfoxide, transiently increases the intracellular calcium ion concentration in various cell types. J Cell Physiol 156:219–225

    Article  CAS  PubMed  Google Scholar 

  • Morris C, de Zreede L, Scholten M, Brand R, van Biezen A, Sureda A, Dickmeiss E, Trneny M, Apperley J, Chiusolo P, van Imhoff GW, Lenhoff S, Martinelli G, Hentrich M, Pabst T, Onida F, Quinn M, Kroger N, de Witte T, Ruutu T, Chronic Malignancies and Lymphoma Working Parties of EBMT (2014) Should the standard dimethyl sulfoxide concentration be reduced? Results of a European Group for Blood and Marrow Transplantation prospective noninterventional study on usage and side effects of dimethyl sulfoxide. Transfusion 54(10):2514–2522

    Article  CAS  PubMed  Google Scholar 

  • Regan DM, Wofford JD, Wall DA (2010) Comparison of cord blood thawing methods on cell recovery, potency, and infusion. Transfusion 50:2670–2675

    Article  PubMed  Google Scholar 

  • Regelson W, Harkins SW (1997) “Amyloid is not a tombstone”-a summation. The primery role for cerebrovascular and CSF dynamics as factors in Alzheimer’s disease (AD): DMSO, fluorocarbon oxygen carriers, thyroid hormonal, and other suggested therapeutic measures. Ann NY Acad Sci 826:348–374

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Delgado GJ, Mancías-Guerra C, Tamez-Gómez EL, Rodríguez-Romo LN, López-Otero A, Hernández-Arizpe A, Gómez-Almanguer D, Ruiz-Argüelles GJ (2009) Dimethyl sulfoxide-induced toxicity in cord blood stem cell transplantation: report of three cases and review of the literature. Acta Haematol 122:1–5

    Article  PubMed  Google Scholar 

  • Santos NC, Figueira-Coelho J, Martins-Silva J, Saldanha C (2003) Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular and molecular aspects. Biochem Pharmacol 65:1035–1041

    Article  CAS  PubMed  Google Scholar 

  • Wolfinbarger LL Jr, Brockbank KGM, Hopkins RA (1989) Application of cryopreservation to heart valves. In: Hopkins RA (ed) Cardiac reconstructions with allograft valves. Springer, Berlin

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. Díaz Rodríguez.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Díaz Rodríguez, R., Van Hoeck, B., De Gelas, S. et al. Determination of residual dimethylsulfoxide in cryopreserved cardiovascular allografts. Cell Tissue Bank 18, 263–270 (2017). https://doi.org/10.1007/s10561-016-9607-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10561-016-9607-0

Keywords

Navigation