Skip to main content
SpringerLink
Log in

Advances in cryopreservation of organs

  • Review
  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

Organ transplantation is an effective approach for the treatment of end-stage organ failures. Currently, the donor organs used for clinical transplantation are all preserved at above-zero temperatures. These preservation methods are well-established and simple but the storage time lasts for only 4–12 h. Some researchers tried to extend the organ storage time by improving protectant and HLA matching to raise the use of stored organs and prolong the long-term survival of organs. These efforts still fall short of the clinical demand for organ transplantation. Moreover, a great many organs were wasted due to limited storage time, HLA mismatch, patients’ conditions or distance involved. Therefore, preserving organs for several weeks or even months and establishing Organ Bank are the tough challenges and have become a shared goal of global scholars. This article reviews some issues involved in the cryopreservation of organs, such as use of cryoprotecting agents, freezing and thawing methods in the cryopreservation of hearts, kidneys and other organs.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Belzer FO, Ashby BS, Dunphy JE. 24-hour and 72-hour preservation of canine kidneys. Lancet, 1967,2(7515): 536–538

    Article  CAS  PubMed  Google Scholar 

  2. Hossain AM, Osuamkpe CO. Sole use of sucrose in human sperm cryopreservation. Arch Androl, 2007, 53(2):99–103

    Article  CAS  PubMed  Google Scholar 

  3. Neronov A, Mazgalova J, Cholakova M, et al. Integrity of endothelium in cryopreserved human cornea. Cryo Letters, 2005,26(2):131–136

    CAS  PubMed  Google Scholar 

  4. Ichikawa H, Takei S, Takashimizu I, et al. Cryopreservation of mouse embryoid bodies. Cryobiology, 2007, 54(3):290–293

    Article  CAS  PubMed  Google Scholar 

  5. Wang X, Chen HF, Yin H, et al. Fertility after intact ovary transplantation. Nature, 2002,415(1):385–386

    Article  CAS  PubMed  Google Scholar 

  6. Ashwood-Smith MJ. Current concepts concerning radioprotective and cryoprotective properties of dimethyl sulfoxide in cellular systems. Ann NY Acad Sci, 1975, 243:246–256

    Article  CAS  PubMed  Google Scholar 

  7. Pegg DE. The role of vitrification techniques of cryopreservation in reproductive medicine. Hum Fertil (Camb), 2005,8(4):231–239

    Article  CAS  Google Scholar 

  8. Wowk B, Leitl E, Rasch CM, et al. Vitrification enhancement by synthetic ice blocking agents, Cryobiology, 2000,40(3):228–236

    Article  CAS  PubMed  Google Scholar 

  9. Wusteman MC, Simmonds J, Vaughan D, et al. Vitrification of rabbit tissues with propylene glycol and trehalose. Cryobiology, 2008,56(1):62–71

    Article  CAS  PubMed  Google Scholar 

  10. Wusteman MC, Pegg DE, Robinson MP, et al. Vitrification media: toxicity, permeability, and dielectric properties. Cryobiology, 2002,44(1):24–37

    Article  CAS  PubMed  Google Scholar 

  11. Wowk B, Darwin M, Harris SB, et al. Effects of solute methoxylation on glass-forming ability and stability of vitrification solutions. Cryobiology, 1999,39(3):215–227

    Article  CAS  PubMed  Google Scholar 

  12. Wusteman M, Rauen U, Simmonds J, et al. Reduction of cryoprotectant toxicity in cells in suspension by use of a sodium-free vehicle solution. Cryobiology, 2008,56(1): 72–79

    Article  CAS  PubMed  Google Scholar 

  13. Fahy GM, Wowk B, Wu J, et al. Improved vitrification solutions based on predictability of vitrification solution toxicity. Cryobiology, 2004,48(1):22–35

    Article  CAS  PubMed  Google Scholar 

  14. Vannereau H, Novakoviteh G, Carin M. Cryobiology of complex tissue. Contracept Fertil Sex, 1998,26(7-8): 573–577

    CAS  PubMed  Google Scholar 

  15. Fahy GM. Analysis of "solution effects" injury: cooling rate dependence of the functional and morphological sequellae of freezing in rabbit renal cortex protected with dimethyl sulfoxide. Cryobiology, 1981,18(6):550–570

    Article  CAS  PubMed  Google Scholar 

  16. Rall WF, Fahy GM. Ice-free cryopreservation of mouse embryos at −196 degrees C by vitrification. Nature, 1985, 313(6003):573–575

    Article  CAS  PubMed  Google Scholar 

  17. Graham LA, Davies PL. Glycine-rich antifreeze proteins from snow fleas. Science, 2005,310(5747):461

    Article  PubMed  Google Scholar 

  18. Celik Y, Drori R, Pertaya-Braun N, et al. Microfluidic experiments reveal that antifreeze proteins bound to ice crystals suffice to prevent their growth. Proc Natl Acad Sci USA, 2013,110(4):1309–1314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yeh CM, Kao BY, Peng HJ. Production of a recombinant type?antifreeze protein analogue by L. lacits and its applications on frozen meat and frozen dough. J Agric Food Chem, 2009,57(14):6216–6223

    CAS  Google Scholar 

  20. Wang Y, Qiu L, Dai C, et al. Expression of insect (Microdera puntipennis dzungarica) antifreeze protein MpAFP149 confers the cold tolerance to transgenic tobacco. Plant Cell Rep, 2008,27(8):1349–1358

    Article  CAS  PubMed  Google Scholar 

  21. Chen L, Li P, Zhao J, et al. Screening of transgenic frost-resistant cotton using a porous silicon biosensing platform. Cryo Letters, 2014,35(1):70–76

    PubMed  Google Scholar 

  22. Cai L, Sun DF, Sun GL. Optimization of a biolistic transformation system for transfer of antifreeze gene KN2 and the bar herbicide resistance gene in common wheat. Genet Mol Res, 2014,13(2):3474–3485

    Article  CAS  PubMed  Google Scholar 

  23. Kamijima T, Sakashita M, Miura A, et al. Antifreeze protein prolongs the life-time of insulinoma cells during hypothermic preservation. PloS One, 2013,8(9):e73643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ideta A, Aoyagi Y, Tsuchiya K, et al. Prolonging hypothermic Storage (4°C) of bovine embryos with fish antifreeze protein. J Reprod Dev, 2015,61(1):1–6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wen Y, Zhao S, Chao L, et al. The protective role of antifreeze protein 3 on the structure and function of mature mouse oocytes in vitrification. Cryobiology, 2014,69(3): 394–401

    Article  CAS  PubMed  Google Scholar 

  26. Jo JW, Jee BC, Lee JR, et al. Effect of antifreeze protein supplementation in vitrification medium on mouse oocyte developmental competence. Fertil Steril, 2011,96(5): 1239–1245

    Article  CAS  PubMed  Google Scholar 

  27. Beirão J, Zilli L, Vilella S, et al. Improving sperm cryopreservation with antifreeze proteins: effect on gilthead seabream (Sparus aurata) plasma membrane lipids. Biol Reprod, 2012,86(2):59

    Article  PubMed  Google Scholar 

  28. Mazur P. Cause of injury in frozen and thawed cells. Fed Proc, 1965,24:S175–S182

    CAS  PubMed  Google Scholar 

  29. Jacobsen IA, Kemp E, Buhl MR. An adverse effect of rapid cooling in kidney preservation. Transplantation, 1979, 27(2):135–136

    CAS  PubMed  Google Scholar 

  30. Rebelo AE, Graham EF, Lillehei RC, et al. Freeze-thaw parameters in successful renal cryopreservation. J Surg Res, 1974,16(1):50–57

    Article  CAS  PubMed  Google Scholar 

  31. Kubota S, Graham F, Crabo BG, et al. The effect of freeze rate, duration of phase transition, and warming rate on survival of frozen canine kidneys. Cryobiology, 1976, 13(4):455–462

    Article  CAS  PubMed  Google Scholar 

  32. Dietzman RH, Kubota S, Rebelo AE, et al. The effect of freezing the kidney on life-supporting function after contralateral nephrectomy. Transplant Proc, 1974,6(3):267–273

    CAS  PubMed  Google Scholar 

  33. Farrant J, Walter CA, Lee H, et al. Use of two-step cooling procedures to examine factors influencing cell survival following freezing and thawing. Cryobiology, 1977,14(3): 273–286

    Article  CAS  PubMed  Google Scholar 

  34. Asahina E. Hisada Y, Emura M. Microscopic observations of innocuous intracellular freezing in very rapidly cooled tumor cells. Contrib Low Temp Sci, 1968,15:36–49

    Google Scholar 

  35. Asahina E, Shimada K, Hisada Y. A stable state of frozen protoplasm with invisible intracellular ice crystals obtained by rapid cooling. Exp Cell Res, 1970,59(3): 349–358

    Article  CAS  PubMed  Google Scholar 

  36. Schmehl MK, Graham EF, Kilkowski SM. Thermographical studies of phantom and canine kidneys thawed by microwave radiation. Cryobiology, 1990,27(3):311–318

    Article  CAS  PubMed  Google Scholar 

  37. Burdette EC, Wiggins S, Brown R, et al. Microwave thawing of frozen kidneys: a theoretically based experimentally-effective design. Cryobiology, 1980,17(4):393–402

    Article  CAS  PubMed  Google Scholar 

  38. Macklis JD, Ketterer FD. Microwave properties of cryoprotectants. Cryobiology, 1978,15(6):627–635

    Article  CAS  PubMed  Google Scholar 

  39. Macklis JD, Ketterer FD, Cravalho EG. Temperature dependence of the microwave properties of aqueous solutions of ethylene glycol between +15 degrees C and −70 degrees C. Cryobiology, 1979,16(3):272–286

    Article  CAS  PubMed  Google Scholar 

  40. Green CJ, Pegg DE. Mechanism of action of “intracellular” renal preservation solutions. World J Surg, 1979,3(1): 115–20, 143-144

    Article  CAS  PubMed  Google Scholar 

  41. Dietzman RH, Rebelo AE, Graham EF, et al. Long-term functional success following freezing of canine kidneys. Surgery, 1973,74(2):181–189

    CAS  PubMed  Google Scholar 

  42. Burdette EC, Wiggins S, Brown R, et al. Microwave thawing of frozen kidneys: a theoretically based experimentally-effective design. Cryobiology, 1980,17(4):393–402

    Article  CAS  PubMed  Google Scholar 

  43. Fahy GM, Ali SE. Cryopreservation of the mammalian kidney II Demonstration of immediate ex vivo function after introduction and removal of 7.5 M cryoprotectant. Cryobiology, 1997,35(2):114–131

    Article  CAS  PubMed  Google Scholar 

  44. Kheirabadi BS, Fahy GM. Permanent life support by kidneys perfused with a vitrifiable (7.5 molar) cryoprotectant solution. Transplantation, 2000,70(1): 51–57

    CAS  PubMed  Google Scholar 

  45. Arnaud FG, Khirabadi B, Fahy GM. Physiological evaluation of a rabbit kidney perfused with VS41A. Cryobiology, 2003, 46 (3):289–294

    Article  CAS  PubMed  Google Scholar 

  46. Fahy GM, Wowk B, Wu J, et al. Improved vitrification solutions based on the predictability of vitrification solution toxicity. Cryobiology, 2004,48(1):22–35

    Article  CAS  PubMed  Google Scholar 

  47. Fahy GM, Wowk B, Wu J, et al. Cryopreservation of organs by vitrification: perspectives and recent advances. Cryobiology, 2004,48(2):157–178

    Article  CAS  PubMed  Google Scholar 

  48. Connaughton PJ, Lewis FJ. Use of glycerol and chloroform in heart preservation by freezing. Surg Forum, 1961, 12:177–179

    CAS  PubMed  Google Scholar 

  49. Robertson RD, Deshpande P, Slegel L, et al. Studies on the function of the canine heart exposed to sub-zero temperatures. JAMA, 1964,187:574–578

    Article  CAS  PubMed  Google Scholar 

  50. Barner HB, Jellinek M, Willman VL, et al. Cardiac perfusion with dextran-dimethyl sulfoxide for cardiac preservation. J Surg Res, 1968,8(8):384–391

    Article  CAS  PubMed  Google Scholar 

  51. Karow AM Jr, Webb WR, Stapp JE. Preservation of hearts by freezing. Arch Surg, 1965,91(4):572–574

    Article  PubMed  Google Scholar 

  52. Karow AM Jr, Carrier O Jr, Holland WC. Toxicity of high dimethyl sulfoxide concentrations in rat heart freezing. Cryobiology, 1967,3(6):464–468

    Article  PubMed  Google Scholar 

  53. Karow AM Jr, Carrier O Jr. Effects of cryoprotectant compounds on mammalian heart muscle. Surg Gynecol Obstet, 1969,128(3):571–583

    CAS  PubMed  Google Scholar 

  54. Armitage WJ, Pegg DE. The contribution of the cryoprotectant to total injury in rabbit hearts frozen with ethylene glycol. Cryobiology, 1979,16(2):152–160

    Article  CAS  PubMed  Google Scholar 

  55. Armitage WJ, Matthes G, Pegg DE. Seleno-DL-methionine reduces freezing injury in hearts protected with ethanediol. Cryobiology, 1981,18(4):370–377

    Article  CAS  PubMed  Google Scholar 

  56. Moss GS, Reed P, Riddell AG. Observations on the effects of glycerol on the cold storage of the canine liver. J Surg Res, 1966,6(4):147–151

    Article  CAS  PubMed  Google Scholar 

  57. Wishnies SM, Parrish AR, Sipes IG, et al. Biotransformation activity in vitrified human liver slices. Cryobiology, 1991,28(3):216–226

    Article  CAS  PubMed  Google Scholar 

  58. Ekins S, Williams JA, Murray GI, et al. Xenobiotic metabolism in rat, dog, and human precision-cut liver slices, freshly isolated hepatocytes, and vitrified precision-cut liver slices. Drug Metab Dispos, 1996,24 (9):990–995

    CAS  PubMed  Google Scholar 

  59. de Graaf IA, Koster HJ. Water crystallization within rat precision-cut liver slices in relation to their viability. Cryobiology, 2001,43(3):224–237

    Article  PubMed  Google Scholar 

  60. Ishihara K, Taniguchi H, Hara Y, et al. Effect of cooling rate of on insulin release from frozen-thawed dispersed rat islet cells. Diabetes Res Clin Pract, 1989,6(4):243–246

    Article  CAS  PubMed  Google Scholar 

  61. Sandler S, Kojima Y, Andersson A. Cryopreservation of mouse pancreatic islets. Effects of fast cooling on islet B cell function and on the outcome of islet transplantation. Transplantation, 1986,42(6):588–593

    CAS  PubMed  Google Scholar 

  62. Fukushima W, Kojima Y, Note M, et al. Cryopreservation of hamster pancreatic islets using a fairly rapid cooling rate. Transplant Proc, 1989,21(1 Pt 3):2641–2643

    CAS  PubMed  Google Scholar 

  63. Warnock GL, Rajotte RV. Effects of precryopreservation culture on survival of rat islets transplanted after slow cooling and rapid thawing. Cryobiology, 1989,26(2): 103–111

    Article  CAS  PubMed  Google Scholar 

  64. Hullett DA, Bethke KP, Landry AS, et al. Successful long-term cryopreservation and transplantation of human fetal pancreas. Diabetes, 1989,38(4):448–453

    Article  CAS  PubMed  Google Scholar 

  65. Kneteman NM, Alderson D, Scharp DW, et al. Long-term cryogenic storage of purified adult human islets of langerhans. Diabetes, 1989,38(3):386–396

    Article  CAS  PubMed  Google Scholar 

  66. Yokogawa Y, Takaki R, Ono J, et al. Cryopreservation of pancreatic islet cells. J Lab Clin Med, 1984,103(5): 768–775

    CAS  PubMed  Google Scholar 

  67. Taylor MJ, Benton MJ. Interaction of cooling rate, warming rate, and extent of permeation of cryoprotectant in determining survival of isolated rat islets of Langerhans during cryopreservaton. Diabetes, 1987,36(1):59–65

    Article  CAS  PubMed  Google Scholar 

  68. Sandler S, Andersson A. Cryopreservation of mouse pancreatic islets: effect of different glucose concentrations in the post-thaw culture medium on islet recovery. Cryobiology, 1987,24(4):285–291

    Article  CAS  PubMed  Google Scholar 

  69. Sugimoto M, Maeda S, Manabe N, et al. Development of infantile rat ovaries autotransplanted after cryopreservation by vitrification. Theriogenology, 2000,53(5):1093–1103

    Article  CAS  PubMed  Google Scholar 

  70. Salehnia M. Autograft of vitrified mouse ovaries using ethylene glycol as cryoprotectant. Exp Anim, 2002,51 (5): 509–512

    Article  CAS  PubMed  Google Scholar 

  71. Segino M, Ikeda M, Aoki S, et al. In vitro culture of mouse GV oocytes and preantral follicles isolated from ovarian tissues cryopreserved by vitrification. Hum Cell, 2003,16(3):109–116

    Article  PubMed  Google Scholar 

  72. Migishima F, Suzuki Migishima R, Song SY, et al. Successful cryopreservation of mouse ovaries by vitrification. Biol Reprod, 2003,68(3):881–887

    Article  CAS  PubMed  Google Scholar 

  73. Kagabu S, Umezu M. Transplantation of cryopreserved mouse, Chinese hamster, rabbit, Japanese monkey and rat ovaries into rat recipients. Exp Anim, 2000,49(1):17–21

    Article  CAS  PubMed  Google Scholar 

  74. Isachenko V, Isachenko E, Rahimi G, et al. Cryopreservation of human ovarian tissue by direct plunging into liquid nitrogen: negative effect of disaccharides in vitrification solution. Cryo Letters, 2002,23(5):333–344

    CAS  PubMed  Google Scholar 

  75. Wang X, Chen H, Yin H, et al. Fertility after intact ovary transplantation. Nature, 2002, 415(6870):385

    Article  CAS  PubMed  Google Scholar 

  76. Perfusix.com, The impact of ex-vivo organ perfusion, http://www.perfusix.com/impact-of-ex-vivo.html. (accessed 3.07.15).

  77. Centers for Disease Control, http://www.cdc.gov/nchs/data/nvsr/nvsr62/nvsr62_06.pdf. (accessed 12.06.15).

  78. Jones B, Bes M. Keeping kidneys, Bull World Health Organ. 2012, 90(10):718–719

    Article  Google Scholar 

  79. Nebraska Organ Recovery, Acceptable Ischemic Times, http://www.nedonation.org/donation-guide/organ/acceptable-ischemic-times. (accessed 3.07.15).

  80. Ardehali A. While millions and millions of lives have been saved, organ transplantation still faces massive problems after 50 years; organ preservation is a big part of the solution, Cryobiology, 2015,71(1):164–165

    Article  Google Scholar 

  81. Khush KK, Zaroff JG, Nguyen J, et al. National decline in donor heart utilization with regional variability: 1995-2010. Am J Transplant, 2015,15(3):642–649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Wohlfahrtova M, Viklicky O. New strategies for evaluating the quality of kidney grafts from elderly donors. Transplant Rev(Orlando), 2015,29(4):212–218

    Article  Google Scholar 

  83. Lewis JK, Bischof JC, Braslavsky I, et al. The Grand Challenges of Organ Banking: Proceedings from the first global summit on complex tissue cryopreservation. Cryobiology. 2015 Dec 12. doi: 10.1016/j.Cryobiol. 2015. 12.001. [Epub ahead of print]

    Google Scholar 

  84. Fahy GM, Wowk B, Wu J. Cryopreservation of complex systems: the missing link in the regenerative medicine supply chain. Rejuvenation Res, 2006,9(2):279–291

    Article  CAS  PubMed  Google Scholar 

  85. de Graaf IA, Draaisma AL, Schoeman O, et al. Cryopreservation of rat precision-cut liver and kidney slices by rapid freezing and vitrification. Cryobiology, 2007, 54(1):1–12

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Union Hospital, Tongji Medical University, Huazhong University of Science and Technology, Wuhan, 430022, China

    Di Liu  (刘 迪) & Feng Pan  (潘 峰)

Authors
  1. Di Liu  (刘 迪)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Feng Pan  (潘 峰)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Feng Pan  (潘 峰).

Additional information

This project was supported by a grant from the Natural Science Foundation of Hubei Province (No. 2011CDB390).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, D., Pan, F. Advances in cryopreservation of organs. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 153–161 (2016). https://doi.org/10.1007/s11596-016-1559-x

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-016-1559-x

Key words

Search

Navigation