Directional Freezing: A Solution to the Methodological Challenges to Preserve Large Organs

ABSTRACT

Although 60 years have passed since the first successful freezing of cells, whole organ freezing is in its initial phase. Heat and mass transfer has limited the success of large tissue and organ cryopreservation either by slow freezing or vitrification. In this article we discuss the limiting factors for the successful freezing of whole organs, such as homogeneous cooling rate, supercooling, latent heat, and recrystallization. We show how the use of directional freezing technology provides solutions to these problems. Whole ovary cryopreservation and transplantation has been proposed as a new method for preserving long-term ovarian function as opposed to ovarian cortical slices. Fertility preservation will benefit from the success of whole ovary freezing and transplantation.

KEYWORDS

Whole ovary - directional freezing - cryopreservation - fertility preservation

REFERENCES

• 1 Polge C, Smith A U, Parkes A S. Revival of spermatozoa after vitrification and dehydration at low temperatures.  Nature. 1949;  164(4172) 666
• 2 Smith A U, Parkes A S. Preservation of ovarian tissue at low temperatures.  Lancet. 1951;  2(6683) 570-572
• 3 Parrott D MV. The fertility of mice with orthotopic ovarian grafts derived from frozen tissue.  J Reprod Fertil. 1960;  1 230-241
• 4 Smith A U. Biological Effects of Freezing and Supercooling. Baltimore, MD; Williams and Wilkins 1961
• 5 Candy C J, Wood M J, Whittingham D G. Follicular development in cryopreserved marmoset ovarian tissue after transplantation.  Hum Reprod. 1995;  10 2334-2338
• 6 Candy C J, Wood M J, Whittingham D G. Restoration of a normal reproductive lifespan after grafting of cryopreserved mouse ovaries.  Hum Reprod. 2000;  15(6) 1300-1304
• 7 Salle B, Demirci B, Franck M, Rudigoz R C, Guerin J F, Lornage J. Normal pregnancies and live births after autograft of frozen-thawed hemi-ovaries into ewes.  Fertil Steril. 2002;  77(2) 403-408
• 8 Almodin C G, Minguetti-Câmara V C, Meister H et al.. Recovery of fertility after grafting of cryopreserved germinative tissue in female rabbits following radiotherapy.  Hum Reprod. 2004;  19(6) 1287-1293
• 9 Donnez J, Dolmans M M, Demylle D et al.. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue.  Lancet. 2004;  364(9443) 1405-1410
• 10 Meirow D, Levron J, Eldar-Geva T et al.. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy.  N Engl J Med. 2005;  353(3) 318-321
• 11 Winston R M, Browne J C. Pregnancy following autograft transplantation of Fallopian tube and ovary in the rabbit.  Lancet. 1974;  2(7879) 494-495
• 12 Goding J R, McCracken J A, Baird D T. The study of ovarian function in the ewe by means of a vascular autotransplantation technique.  J Endocrinol. 1967;  39(1) 37-52
• 13 Paldi E, Gal D, Barzilai A, Hampel N, Malberger E. Genital organs. Auto and homotransplantation in forty dogs.  Int J Fertil. 1975;  20(1) 5-12
• 14 Scott J R, Keye W R, Poulson A M, Reynolds W A. Microsurgical ovarian transplantation in the primate.  Fertil Steril. 1981;  36(4) 512-515
• 15 Leporrier M, von Theobald P, Roffe J L, Muller G. A new technique to protect ovarian function before pelvic irradiation. Heterotopic ovarian autotransplantation.  Cancer. 1987;  60(9) 2201-2204
• 16 Arav A, Elami A, Bor A et al.. Successful whole organ cryopreservation and transplantation [abstract]. Paper presented at: Annual Meeting of the American Society for Reproductive Medicine October 21–24, 2001 Orlando, FL;
• 17 Revel A, Elami A, Bor A et al.. Whole ovary cryopreservation and transplantation.  Fertil Steril. 2004;  82 1714-1715
• 18 Wang X, Chen H, Yin H, Kim S S, Lin Tan S, Gosden R G. Fertility after intact ovary transplantation.  Nature. 2002;  415(6870) 385
• 19 Chen C, Chen S, Chang F, Wu G, Liu J, Yu C. Autologous heterotopic transplantation of intact rabbit ovary after cryopreservation.  Hum Reprod. 2005;  20(suppl 1) i145-i150
• 20 Arav A, Revel A, Nathan Y et al.. Oocyte recovery, embryo development and ovarian function after cryopreservation and transplantation of whole sheep ovary.  Hum Reprod. 2005;  20(12) 3554-3559
• 21 Mazur P. Cryobiology: the freezing of biological systems.  Science. 1970;  168(934) 939-949
• 22 Karlsson J O, Toner M. Long-term storage of tissues by cryopreservation: critical issues.  Biomaterials. 1996;  17(3) 243-256
• 23 Pegg D E, Wang L, Vaughan D, Hunt C J. Cryopreservation of articular cartilage. Part 2: mechanisms of cryoinjury.  Cryobiology. 2006;  52(3) 347-359
• 24 Hubel A, Toner M, Cravalho E G, Yarmush M L, Tompkins R G. Intracellular ice formation during the freezing of hepatocytes cultured in a double collagen gel.  Biotechnol Prog. 1991;  7(6) 554-559
• 25 Yavin S, Arav A. Measurement of essential physical properties of vitrification solutions.  Theriogenology. 2007;  67(1) 81-89
• 26 Fahy G M, Saur J, Williams R J. Physical problems with the vitrification of large biological systems.  Cryobiology. 1990;  27(5) 492-510
• 27 Forsyth M, MacFarlane D R. Recrystallization revisited.  Cryo Lett. 1986;  7 367-378
• 28 Gacitua H, Arav A. Successful pregnancies with directional freezing of large volume buck semen.  Theriogenology. 2005;  63(3) 931-938
• 29 Diller K R. Modeling of bioheat transfer processes at high and low temperatures. In: Cho YI Bioengineering Heat Transfer. Vol. 221. San Diego, CA; Academic Press 1992: 157-357
• 30 Mazur P. Theoretical and experimental effects of cooling and warming velocity on the survival of frozen and thawed cells.  Cryobiology. 1966;  2(4) 181-192
• 31 Keobe H G, Werner A, Lange V, Schildberg F W. Temperature gradients in freezing chambers of rate-controlled cooling machines.  Cryobiology. 1993;  30 349-352
• 32 Arav A, Yavin S, Zeron Y, Natan D, Dekel I, Gacitua H. New trends in gamete's cryopreservation.  Mol Cell Endocrinol. 2002;  187(1-2) 77-81
• 33 Arav A. Large tissue freezing.  J Assist Reprod Genet. 2003;  20(9) 351