Successful preservation of canine small intestine by freezing

Hamilton, Richard T.; Holst, Hazel I.; Lehr, Herndon B.

doi:10.1016/0022-4804(73)90033-4

Cited by 13 publications

(6 citation statements)

References 10 publications

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“…Biobanking of organ and tissue replacements has not been widely discussed perhaps in part because the technology for doing this without damage to the graft is not in hand. Although freezing can achieve limited success for some organs, 7,9,[12][13][14][15] freezing of the heart, liver or kidney has not been accomplished with subsequent life support function following cooling to temperatures low enough for long-term preservation, despite work on this problem dating back to the 1950s. 3,6 Kidneys and hearts have been the most widely studied organs, but neither has been reproducibly recovered after freezing to temperatures lower than about -20°C, [16][17][18][19][20] evidently due at least in part to mechanical damage from ice itself, [21][22][23][24] although in the case of kidneys at least, sporadic survival has sometimes been claimed after freezing to about -40 to -80°C.…”

Section: Introductionmentioning

confidence: 99%

Physical and biological aspects of renal vitrification

et al. 2009

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Cryopreservation would potentially very much facilitate the inventory control and distribution of laboratory-produced organs and tissues. Although simple freezing methods are effective for many simple tissues, bioartificial organs and complex tissue constructs may be unacceptably altered by ice formation and dissolution. Vitrification, in which the liquids in a living system are converted into the glassy state at low temperatures, provides a potential alternative to freezing that can in principle avoid ice formation altogether. The present report provides a brief overview of the problem of renal vitrification. We report here the detailed case history of a rabbit kidney that survived vitrification and subsequent transplantation, a case that demonstrates both the fundamental feasibility of complex system vitrification and the obstacles that must still be overcome, of which the chief one in the case of the kidney is adequate distribution of cryoprotectant to the renal medulla. Medullary equilibration can be monitored by monitoring urine concentrations of cryoprotectant, and urine flow rate correlates with vitrification solution viscosity and the speed of equilibration. By taking these factors into account and by using higher perfusion pressures as per the case of the kidney that survived vitrification, it is becoming possible to design protocols for equilibrating kidneys that protect against both devitrification and excessive cryoprotectant toxicity.

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Section: Introductionmentioning

confidence: 99%

Physical and biological aspects of renal vitrification

et al. 2009

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“…Hamilton, Holst, and Lehr achieved the next major breakthrough in 1973, freezing lengths of dog intestine in liquid nitrogen, thawing them, and obtaining long-term survival of a minority of these segments after transplantation. 32 In 2002, considerable attention was given to a report of partial success with intact rat ovaries 33 that were frozen, thawed, and transplanted by vascular anastomosis. A minority of these ovaries survived, but one survivor was able to give rise to developing pups.…”

Section: Organ Cryopreservation By Freezingmentioning

confidence: 99%

Cryopreservation of Complex Systems: The Missing Link in the Regenerative Medicine Supply Chain

Fahy

Wowk

2006

Rejuvenation Research

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Transplantation can be regarded as one form of "antiaging medicine" that is widely accepted as being effective in extending human life. The current number of organ transplants in the United States is on the order of 20,000 per year, but the need may be closer to 900,000 per year. Cadaveric and living-related donor sources are unlikely to be able to provide all of the transplants required, but the gap between supply and demand can be eliminated in principle by the field of regenerative medicine, including the present field of tissue engineering through which cell, tissue, and even organ replacements are being created in the laboratory. If so, it could allow over 30% of all deaths in the United States to be substantially postponed, raising the probability of living to the age of 80 by a factor of two and the odds of living to 90 by more than a factor of 10. This promise, however, depends on the ability to physically distribute the products of regenerative medicine to patients in need and to produce these products in a way that allows for adequate inventory control and quality assurance. For this purpose, the ability to cryogenically preserve (cryopreserve) cells, tissues, and even whole laboratory-produced organs may be indispensable. Until recently, the cryopreservation of organs has seemed a remote prospect to most observers, but developments over the past few years are rapidly changing the scientific basis for preserving even the most difficult and delicate organs for unlimited periods of time. Animal intestines and ovaries have been frozen, thawed, and shown to function after transplantation, but the preservation of vital organs will most likely require vitrification. With vitrification, all ice formation is prevented and the organ is preserved in the glassy state below the glass transition temperature (T G ). Vitrification has been successful for many tissues such as veins, arteries, cartilage, and heart valves, and success has even been claimed for whole ovaries. For vital organs, a significant recent milestone for vitrification has been the ability to routinely recover rabbit kidneys after cooling to a mean intrarenal temperature of about Ϫ45°C, as verified by life support function after transplantation. This temperature is not low enough for long-term banking, but research continues on preservation below Ϫ45°C, and some encouraging preliminary evidence has been obtained indicating that kidneys can support life after vitrification. Full development of tissue engineering and organ generation from stem cells, when combined with the ability to bank these laboratory-produced products, in theory could dramatically increase median life expectancy even in the absence of any improvements in mitigating aging processes on a fundamental level. 279

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“…Prior cryogenic organ preservation efforts have typically (although not universally [36]) encountered either lethal [14,15] or unacceptably damaging [16,37–39] amounts of extracellular ice, or the challenge of introducing the enormous concentrations of CPA needed to preclude such damage [16,40,41]. So far, these difficult challenges have not been adequately overcome, and therefore, other approaches should be investigated and may produce practical results more rapidly.…”

Section: Discussionmentioning

confidence: 99%

“…For liver transplantation, lengthening the allograft preservation time from the current standard of SCS at 4°C will reduce the burden placed on the healthcare system from high costs of unplanned surgeries, decrease organ rejection rates by incorporating more HLA typing into clinical practice, and possibly even open avenues for global matching programs [3,35]. Prior cryogenic organ preservation efforts have typically (although not universally [36]) encountered either lethal [14,15] or unacceptably damaging [16,[37][38][39] amounts of extracellular ice, or the challenge of introducing the enormous concentrations of CPA needed to preclude such damage [16,40,41]. So far, these difficult challenges have not been adequately overcome, and therefore, other approaches should be investigated and may produce practical results more rapidly.…”

Section: Discussionmentioning

confidence: 99%

The role of antifreeze glycopeptides (AFGP) and polyvinyl alcohol/polyglycerol (X/Z-1000) cocktails as ice modulators during partial freezing of rat livers

Tessier

Haque

Pendexter

et al. 2021

Preprint

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The current liver organ shortage has pushed the field of liver transplantation to develop new methods to prolong the preservation time of livers from the current clinical standard of static cold storage. Our approach, termed partial freezing, aims to induce a thermodynamically stable frozen state at deeper storage temperatures (–10°C to –15°C) than can be achieved with supercooling, while simultaneously maintaining a sufficient unfrozen fraction to limit dehydration and ice damage. This research first demonstrated that partially frozen glycerol treated rat livers were functionally similar after thawing from either –10 or –15°C with respect to subnormothermic machine perfusion metrics and histology. Next, we assessed the effect of adding either of two ice modulators, antifreeze glycoprotein (AFGP) and a polyvinyl alcohol/polyglycerol combination (X/Z-1000), on the viability and structural integrity of partially frozen rat livers compared to glycerol-only control livers. Results showed that AFGP livers had high levels of ATP and the least edema but suffered from significant endothelial cell damage. X/Z-1000 livers had the highest levels of ATP and energy charge (EC) but also demonstrated endothelial damage and post-thaw edema. Glycerol-only control livers exhibited the least DNA damage on Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining but also had the lowest levels of ATP and EC. Further research is necessary to optimize the ideal ice modulator cocktail for our partial-freezing protocol. Modifications to cryoprotective agent (CPA) combinations, as well as improvements to machine perfusion CPA loading and unloading, can help improve the viability of these partially frozen organs.

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Successful preservation of canine small intestine by freezing

Cited by 13 publications

References 10 publications

Physical and biological aspects of renal vitrification

Physical and biological aspects of renal vitrification

Cryopreservation of Complex Systems: The Missing Link in the Regenerative Medicine Supply Chain

The role of antifreeze glycopeptides (AFGP) and polyvinyl alcohol/polyglycerol (X/Z-1000) cocktails as ice modulators during partial freezing of rat livers

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