- Email: [email protected]
60. Innovative cryoprotectants for tissue and organ preservation
180
Abstracts / Cryobiology 71 (2015) 164–180
for donation, there is time to induce protein production and for the proteins to take effect. Going forward, suitable animal models should be developed to assess the effectiveness of externally induced in vivo preconditioning. An ethical debate is needed to address whether the extra physical and chemical stress that the beating heart donors will have to undergo is justifiable. In conclusion, under the current algorithm for organ donation, valuable time and treatment opportunities for organ preconditioning are unutilized during the period of time while beating heart donors are awaiting organ procurement. The physiological environment in heart beating donors enables treatment options that cannot be provided by extracorporeal perfusion systems after explantation. Therefore, utilizing the donor body for preconditioning of the organs may enable new protocols that are less toxic and reduce the duration of ex vivo preconditioning to ultimately facilitate success in cryopreservation.
extracellular nucleation had been triggered the careful control of temperature would be needed to ensure optimal dehydration of cells for successful cryopreservation. It is anticipated that the size of crystals can be tuned by varying the concentration of ice nucleating particles. On rewarming, a uniform ice crystal size will prevent excessive recrystallization of large ice crystals and the ensuing tissue damage that is often observed during vitrification procedures. Overall, it might be possible to use a controlled rate freezing type method with larger, more complex systems than is currently possible. Although such an approach provides numerous potential benefits there are many uncertainties that will need to be explored through experiment. It is proposed that such experiments could start with light microscopy of dyed cryoprotectant solutions to determine if ice crystals of suitably small size can indeed be formed before moving onto cell suspensions, tissues and whole organs.
http://dx.doi.org/10.1016/j.cryobiol.2015.05.064
http://dx.doi.org/10.1016/j.cryobiol.2015.05.065
59. High concentration ice nucleation for controlled rate freezing of complex biological systems. Thomas Whale a, Michael Chasnitsky b, Leela Tanikella c, Maximilian Kueckelhaus d, a School of Earth and Environment, University of Leeds, UK, b Racah Institute of Physics, Hebrew University of Jerusalem, Israel, c Berkeley College of Engineering, University of California, CA, USA, d Harvard Medical School, Boston, MA, USA
60. Innovative cryoprotectants for tissue and organ preservation. Mark Kline a,1,2, Mats Dreyer b,1,2, Peter Gyring c,1,2, Mark Lifson d,2, Rami El Assal d,1,2, a Molecular Foundry, Biological Nanostructures Facility, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA, b Fung Institute, University of California Berkeley, Berkeley, CA 94704, USA, c Institute of Biomedical Engineering, University of Oxford, Oxford OX3 7DQ, UK, d Canary Center for Early Cancer Detection, Department of Radiology, School of Medicine, Stanford University, Palo Alto, CA 94304, USA Email address: [email protected]
Cryopreservation of human organs would facilitate long term organ banking and potentially go a long way to remedying the global shortage of organs for transplantation. To date, almost all attempts at cryopreservation of whole organs have used vitrification methods. Controlled rate freezing, which is commonly used for freezing of various types of cell suspensions, is unlikely to work well for whole organs as ice crystals will inevitably nucleate and grow to damaging sizes. Here, we propose an alternative to vitrification for the cryopreservation of whole organs. By introducing very large numbers of small ice nucleating particles to an organ it might be possible to induce formation of very large numbers of small, relatively harmless crystals, rather than small numbers of large, and therefore damaging ice crystals. The ice nucleating particles used would have to be less than 50 nm in diameter, and would have to nucleate ice at a high and very uniform temperature. The minimum known size of effective ice nucleating particles has been falling rapidly of late, meaning that particles of the requisite size and effectiveness are now known, although it is likely that further work will have to be conducted to generate sufficiently uniform ice nucleation temperatures. Uniformity of crystal size is of vital importance as larger ice crystals are more thermodynamically stable than smaller ones and as such will tend to grow at the expense of smaller crystals, rapidly producing ice of a damaging size. To achieve this, an organ would need to be supercooled very uniformly so that nucleation occurred at a similar time throughout. Once
The need to cryopreserve living tissues and organs is an escalating clinical problem in modern transplantation and regenerative medicine. Existing cryopreservation techniques utilize freezing or vitrification strategies for preservation of tissues and organs. These approaches use cryoprotactants such as dimethyl sulfoxide and glycerol that are toxic and not very effective at low concentrations. Here, we propose to use an innovative approach that integrates bio-inspired and dynamic-hydrogel cryoprotectants for tissue and organ preservation. This approach has the potential to address current challenges in tissue and organ banking as well as enable new clinical applications, including cryopreserving patient-specific tissues for drug-screening and personalized medicine.
1 2
Contributed by participating in the hackathon competition. Contributed by participating in the abstract.
http://dx.doi.org/10.1016/j.cryobiol.2015.05.066
Abstracts / Cryobiology 71 (2015) 164–180
for donation, there is time to induce protein production and for the proteins to take effect. Going forward, suitable animal models should be developed to assess the effectiveness of externally induced in vivo preconditioning. An ethical debate is needed to address whether the extra physical and chemical stress that the beating heart donors will have to undergo is justifiable. In conclusion, under the current algorithm for organ donation, valuable time and treatment opportunities for organ preconditioning are unutilized during the period of time while beating heart donors are awaiting organ procurement. The physiological environment in heart beating donors enables treatment options that cannot be provided by extracorporeal perfusion systems after explantation. Therefore, utilizing the donor body for preconditioning of the organs may enable new protocols that are less toxic and reduce the duration of ex vivo preconditioning to ultimately facilitate success in cryopreservation.
extracellular nucleation had been triggered the careful control of temperature would be needed to ensure optimal dehydration of cells for successful cryopreservation. It is anticipated that the size of crystals can be tuned by varying the concentration of ice nucleating particles. On rewarming, a uniform ice crystal size will prevent excessive recrystallization of large ice crystals and the ensuing tissue damage that is often observed during vitrification procedures. Overall, it might be possible to use a controlled rate freezing type method with larger, more complex systems than is currently possible. Although such an approach provides numerous potential benefits there are many uncertainties that will need to be explored through experiment. It is proposed that such experiments could start with light microscopy of dyed cryoprotectant solutions to determine if ice crystals of suitably small size can indeed be formed before moving onto cell suspensions, tissues and whole organs.
http://dx.doi.org/10.1016/j.cryobiol.2015.05.064
http://dx.doi.org/10.1016/j.cryobiol.2015.05.065
59. High concentration ice nucleation for controlled rate freezing of complex biological systems. Thomas Whale a, Michael Chasnitsky b, Leela Tanikella c, Maximilian Kueckelhaus d, a School of Earth and Environment, University of Leeds, UK, b Racah Institute of Physics, Hebrew University of Jerusalem, Israel, c Berkeley College of Engineering, University of California, CA, USA, d Harvard Medical School, Boston, MA, USA
60. Innovative cryoprotectants for tissue and organ preservation. Mark Kline a,1,2, Mats Dreyer b,1,2, Peter Gyring c,1,2, Mark Lifson d,2, Rami El Assal d,1,2, a Molecular Foundry, Biological Nanostructures Facility, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA, b Fung Institute, University of California Berkeley, Berkeley, CA 94704, USA, c Institute of Biomedical Engineering, University of Oxford, Oxford OX3 7DQ, UK, d Canary Center for Early Cancer Detection, Department of Radiology, School of Medicine, Stanford University, Palo Alto, CA 94304, USA Email address: [email protected]
Cryopreservation of human organs would facilitate long term organ banking and potentially go a long way to remedying the global shortage of organs for transplantation. To date, almost all attempts at cryopreservation of whole organs have used vitrification methods. Controlled rate freezing, which is commonly used for freezing of various types of cell suspensions, is unlikely to work well for whole organs as ice crystals will inevitably nucleate and grow to damaging sizes. Here, we propose an alternative to vitrification for the cryopreservation of whole organs. By introducing very large numbers of small ice nucleating particles to an organ it might be possible to induce formation of very large numbers of small, relatively harmless crystals, rather than small numbers of large, and therefore damaging ice crystals. The ice nucleating particles used would have to be less than 50 nm in diameter, and would have to nucleate ice at a high and very uniform temperature. The minimum known size of effective ice nucleating particles has been falling rapidly of late, meaning that particles of the requisite size and effectiveness are now known, although it is likely that further work will have to be conducted to generate sufficiently uniform ice nucleation temperatures. Uniformity of crystal size is of vital importance as larger ice crystals are more thermodynamically stable than smaller ones and as such will tend to grow at the expense of smaller crystals, rapidly producing ice of a damaging size. To achieve this, an organ would need to be supercooled very uniformly so that nucleation occurred at a similar time throughout. Once
The need to cryopreserve living tissues and organs is an escalating clinical problem in modern transplantation and regenerative medicine. Existing cryopreservation techniques utilize freezing or vitrification strategies for preservation of tissues and organs. These approaches use cryoprotactants such as dimethyl sulfoxide and glycerol that are toxic and not very effective at low concentrations. Here, we propose to use an innovative approach that integrates bio-inspired and dynamic-hydrogel cryoprotectants for tissue and organ preservation. This approach has the potential to address current challenges in tissue and organ banking as well as enable new clinical applications, including cryopreserving patient-specific tissues for drug-screening and personalized medicine.
1 2
Contributed by participating in the hackathon competition. Contributed by participating in the abstract.
http://dx.doi.org/10.1016/j.cryobiol.2015.05.066