Groundbreaking technology rewarms large-scale animal tissues preserved at low temperatures
A major step toward long-term preservation of organs and tissues for transplantation; could lead to saving millions of human lives
March 2, 2017
Inductive radio-frequency heating of magnetic nanoparticles embedded in tissue (red material in container) preserved at very low temperatures restored the tissue without damage (credit: Navid Manuchehrabadi et al./Science Translational Medicine)
A research team led by the University of Minnesota has discovered a way to rewarm large-scale animal heart valves and blood vessels preserved at very low (cryogenic) temperatures without damaging the tissue. The discovery could one day lead to saving millions of human lives by creating cryogenic tissue and organ banks of organs and tissues for transplantation.
The research was published March 1 in an open-access paper in Science Translational Medicine.
Long-term preservation methods like vitrification cool biological samples to an ice-free glassy state, using very low temperatures between -160 and -196 degrees Celsius, but tissues larger than 1 milliliter (0.03 fluid ounce) often suffer major damage during the rewarming process, making them unusable for tissues.
In the new research, the researchers were able to restore 50 milliliters (1.7 fluid ounces) of tissue with warming at more than 130°C/minute without damage.
Radiofrequency inductive heating of iron nanoparticles
To achieve that, they developed a revolutionary new method using silica-coated iron-oxide nanoparticles dispersed throughout a cryoprotectant solution around the tissue. The nanoparticles act as tiny heaters around the tissue when they are activated using noninvasive radiofrequency inductive energy, rapidly and uniformly warming the tissue.
This transmission electron microscopy (TEM) image shows the iron oxide nanoparticles (coated in mesoporous silica) that are used in the tissue warming process. (credit: Haynes research group/University of Minnesota)
The results showed that none of the tissues displayed signs of harm — unlike control samples using vitrification and rewarmed slowly over ice or using convection warming. The researchers were also able to successfully wash away the iron oxide nanoparticles from the sample following the warming.
“This is the first time that anyone has been able to scale up to a larger biological system and demonstrate successful, fast, and uniform warming of hundreds of degrees Celsius per minute of preserved tissue without damaging the tissue,” said University of Minnesota mechanical engineering and biomedical engineering professor John Bischof, the senior author of the study.
Bischof said there is a strong possibility they could scale up to even larger systems, like organs. The researchers plan to start with rodent organs (such as rat and rabbit) and then scale up to pig organs and then, hopefully, human organs. The technology might also be applied beyond cryogenics, including delivering lethal pulses of heat to cancer cells.
The researchers’ goal is to eliminate transplant waiting lists. Currently, hearts and lungs donated for transplantation must be discarded because these tissues cannot be kept on ice for longer than a matter of hours, according to the researchers.*
It will be interesting to see if the technology can one day be extended to cryonics.
The research was funded by the National Science Foundation (NSF), National Institutes of Health (NIH), U.S. Army Medical Research and Materiel Command, Minnesota Futures Grant from the University of Minnesota, and the University of Minnesota Carl and Janet Kuhrmeyer Chair in Mechanical Engineering. Researchers at Carnegie Mellon University, Clemson University and Tissue Testing Technologies LLC were also involved in the study.
* “A major limitation of transplantation is the ischemic injury that tissue and organs sustain during the time between recovery from the donor and implantation in the recipient. The maximum tolerable organ preservation for transplantation by hypothermic storage is typically 4 hours for heart and lungs; 8 to 12 hours for liver, intestine, and pancreas; and up to 36 hours for kidney transplants. In many cases, such limits actually prevent viable tissue or organs from reaching recipients. For instance, more than 60% of donor hearts and lungs are not used or transplanted partly because their maximum hypothermic preservation times have been exceeded. Further, if only half of these discarded organs were transplanted, then it has been estimated that wait lists for these organs could be extinguished within 2 to 3 years.” — Navid Manuchehrabadi et al./Science Translational Medicine
Abstract of Improved tissue cryopreservation using inductive heating of magnetic nanoparticles
Vitrification, a kinetic process of liquid solidification into glass, poses many potential benefits for tissue cryopreservation including indefinite storage, banking, and facilitation of tissue matching for transplantation. To date, however, successful rewarming of tissues vitrified in VS55, a cryoprotectant solution, can only be achieved by convective warming of small volumes on the order of 1 ml. Successful rewarming requires both uniform and fast rates to reduce thermal mechanical stress and cracks, and to prevent rewarming phase crystallization. We present a scalable nanowarming technology for 1- to 80-ml samples using radiofrequency-excited mesoporous silica–coated iron oxide nanoparticles in VS55. Advanced imaging including sweep imaging with Fourier transform and microcomputed tomography was used to verify loading and unloading of VS55 and nanoparticles and successful vitrification of porcine arteries. Nanowarming was then used to demonstrate uniform and rapid rewarming at >130°C/min in both physical (1 to 80 ml) and biological systems including human dermal fibroblast cells, porcine arteries and porcine aortic heart valve leaflet tissues (1 to 50 ml). Nanowarming yielded viability that matched control and/or exceeded gold standard convective warming in 1- to 50-ml systems, and improved viability compared to slow-warmed (crystallized) samples. Last, biomechanical testing displayed no significant biomechanical property changes in blood vessel length or elastic modulus after nanowarming compared to untreated fresh control porcine arteries. In aggregate, these results demonstrate new physical and biological evidence that nanowarming can improve the outcome of vitrified cryogenic storage of tissues in larger sample volumes.
- Navid Manuchehrabadi, Zhe Gao, Jinjin Zhang, Hattie L. Ring, Qi Shao, Feng Liu, Michael McDermott, Alex Fok, Yoed Rabin, Kelvin G. M. Brockbank, Michael Garwood, Christy L. Haynes, John C. Bischof. Improved tissue cryopreservation using inductive heating of magnetic nanoparticles. Science Translational Medicine01 Mar 2017; DOI: 10.1126/scitranslmed.aah4586 (open access)
Topics: Biomed/Longevity | Electronics | Nanotech/Materials Science
Mayo Clinic discovers high-intensity aerobic training can reverse aging
March 24, 2017
Mayo Clinic study finds high-intensity aerobic exercise may reverse aging (credit: Flickr user Global Panorama via Creative Commons license)
A Mayo Clinic study says the best training for adults is high-intensity aerobic exercise, which they believe can reverse some cellular aspects of aging.
Mayo researchers compared 12 weeks of high-intensity interval training (workouts in which you alternate periods of high-intensity exercise with low-intensity recovery periods), resistance training, and combined training. While all three enhanced insulin sensitivity and lean mass, only high-intensity interval training and combined training improved aerobic capacity and skeletal muscle mitochondrial respiration. (Decline in mitochondrial content and function are common in older adults.)
High-intensity intervals also improved muscle protein content, which enhanced energetic functions and also caused muscle enlargement, especially in older adults. The researchers said exercise training significantly enhanced the cellular machinery responsible for making new proteins. That contributes to protein synthesis, thus reversing a major adverse effect of aging.
12 weeks exercise training in younger and older people (credit: Mayo Clinic)
“We encourage everyone to exercise regularly, but the take-home message for aging adults is that supervised high-intensity training is probably best, because, both metabolically and at the molecular level, it confers the most benefits,” says K. Sreekumaran Nair, M.D., Ph.D., a Mayo Clinic endocrinologist and senior researcher on the study.
He says the high-intensity training reversed some manifestations of aging in the body’s protein function, but noted that increasing muscle strength requires resistance training a couple of days a week.
In the study, researchers tracked metabolic and molecular changes in a group of young and older adults over 12 weeks, gathering data 72 hours after individuals in randomized groups completed each type of exercise. General findings showed:
- Cardio respiratory health, muscle mass, and insulin sensitivity improved with all training.
- Mitochondrial cellular function declined with age but improved with training.
- Increase in muscle strength occurred only modestly with high-intensity interval training, but occurred with resistance training alone or when added to the aerobic training.
- Exercise improves skeletal muscle gene expression independent of age.
- Exercise substantially enhanced the ribosomal proteins responsible for synthesizing new proteins, which is mainly responsible for enhanced mitochondrial function.
- Training has no significant effect on skeletal muscle DNA epigenetic changes but promotes skeletal muscle protein expression with maximum effect in older adults.
The research findings appear in Cell Metabolism. The research was supported by the National Institutes of Health, Mayo Clinic, the Robert and Arlene Kogod Center on Aging, and the Murdock-Dole Professorship.
Abstract of Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans
The molecular transducers of benefits from different exercise modalities remain incompletely defined. Here we report that 12 weeks of high-intensity aerobic interval (HIIT), resistance (RT), and combined exercise training enhanced insulin sensitivity and lean mass, but only HIIT and combined training improved aerobic capacity and skeletal muscle mitochondrial respiration. HIIT revealed a more robust increase in gene transcripts than other exercise modalities, particularly in older adults, although little overlap with corresponding individual protein abundance was noted. HIIT reversed many age-related differences in the proteome, particularly of mitochondrial proteins in concert with increased mitochondrial protein synthesis. Both RT and HIIT enhanced proteins involved in translational machinery irrespective of age. Only small changes of methylation of DNA promoter regions were observed. We provide evidence for predominant exercise regulation at the translational level, enhancing translational capacity and proteome abundance to explain phenotypic gains in muscle mitochondrial function and hypertrophy in all ages.
- Robinson, Matthew M. et al. Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans. Cell Metabolism , Volume 25 , Issue 3 , 581 - 592; DOI: 10.1016/j.cmet.2017.02.009
Scientists discover precise DNA sequence code critical for turning genes on
Geneticists solve a decades-long puzzle about how genes are turned on to make cellular proteins
January 27, 2017
DNA sequence signal for the activation of human genes. Each tiny human cell contains about six feet of DNA, a double-helical molecular chain containing four types of several billion chemical nucleotides — adenine (A), cytosine (C), guanine (G) and thymine (T) — arranged in a specific sequence, or code, that when transcribed guide the cell into producing specific proteins. (credit: University of California — San Diego)