New computer model is a key step toward low-temperature preservation of
3D tissues, organs
Date:
November 10, 2021
Source:
Oregon State University
Summary:
Medical science is a key step closer to the cryopreservation of
brain slices used in neurological research, pancreatic cells for
the treatment of diabetes and even whole organs thanks to a new
computer model that predicts how tissue's size will change during
the preservation process.
FULL STORY ========================================================================== Medical science is a key step closer to the cryopreservation of brain
slices used in neurological research, pancreatic cells for the treatment
of diabetes and even whole organs thanks to a new computer model that
predicts how tissue's size will change during the preservation process.
========================================================================== Findings of the study led by Adam Higgins of the Oregon State University College of Engineering were published in Biophysical Journal.
"Cryopreservation of tissues would be useful for biomedical research
and for transplantation medicine, but it's difficult to cryopreserve
tissues for various reasons," said Higgins, associate professor of bioengineering. "A major reason is that formation of ice can break apart
a tissue from the inside. Folks who cook are probably already familiar
with this -- a tomato that has been frozen and thawed becomes mushy." Cryopreservation has long been widely used in comparatively simpler applications such as preserving semen, blood, embryos and plant seeds. A barrier to other uses has been damage from ice crystallization and the
harmful nature of the compounds added to prevent ice formation.
Vitrification, Higgins explains, is a cryopreservation strategy that
thwarts ice crystal damage through chemicals known as cryoprotectants,
or CPAs, that can keep ice from forming. An example of a CPA is ethylene glycol, used in automobile antifreeze.
In tissues, a high enough concentration of CPAs causes a solid "glass" to
form rather than ice crystals when tissue temperature is reduced to liquid nitrogen levels; liquid nitrogen boils at minus-320 degrees Fahrenheit.
==========================================================================
"The problem is that these chemicals can cause osmotic damage due to
water crossing cell membranes and causing the cells to burst," Higgins
said. "They can also kill cells due to toxicity. So in designing the
best vitrification method, the trick is choosing the best path between
normal physiological conditions and a final vitrified state -- i.e.,
high CPA concentration and liquid nitrogen temperature." Hence the need
for mathematical modeling. In earlier research involving a single layer
of endothelial cells, which make up the lining of the circulatory system, Higgins and colleagues in the College of Engineering showed the value of
a model that involved CPA toxicity, osmotic damage and mass transfer. The modeling uncovered an approach for loading CPA that was counterintuitive: inducing cells to swell.
The researchers found that if cells were initially exposed to a low CPA concentration and given time to swell, the sample could be vitrified after rapidly adding a high concentration. The upshot was much less overall
toxicity, Higgins said. Healthy cell survival following vitrification
rose from about 10% with a conventional approach to greater than 80%.
"The biggest single problem and limiting factor in vitrification is CPA toxicity and the swelling method was quite useful for addressing that,"
he said. "Our new paper extends this line of research by presenting a
new model of mass transfer in tissue; a key feature is that it allows
for the prediction of tissue size changes." Higgins notes that there
have been observations of multiple types of tissues changing size after exposure to CPA solutions; among them are cartilage, ovarian tissue and
groups of cell in the pancreas known as islets. More likely than not,
those size changes are important considerations for the design of methods
for tissue vitrification, he said.
==========================================================================
"The conventional mass transfer modeling approach is known as Fick's law
and that assumes tissue size remains constant," Higgins said. "Our new
model, which we used for two very different types of tissues, articular cartilage and pancreatic islets, opens the door to extending our previous mathematical optimization approach to the design of better methods for
the cryopreservation of various tissue types." As vitrification of increasingly complex tissues becomes possible, new applications for it
are likely to become feasible, Higgins said -- especially as progress
continues in the quickly advancing field of tissue regeneration, in
which stem cells can be used to grow new tissues or even whole organs.
Conceivably, he said, tissues could be made in small amounts and stored
until needed for transplantation. Organs donated for transplants could be routinely preserved until a precise immunological match was found. It's
also not outside the realm of possibility, Higgins said, that people
could grow a backup heart or liver from their own stem cells and have
it vitrified for future use as needed.
Drug development is another area that would benefit from improved and
expanded vitrification potential, he added.
Drug testing typically occurs within traditional cell culture systems
or in animal models, which often don't accurately predict the effect
of the drug in people. New "organs on a chip" -- microfluidic chambers containing human cells cultured under conditions that mimic native tissues
or organs -- might be able to more accurately forecast drug responses
in people, but their use necessitates cells being stored long term as vitrification allows.
Collaborating with Higgins were Ross Warner, a research associate in the
OSU College of Engineering, Ali Eroglu of Augusta University in Georgia
and Robyn Shuttleworth and James Benson of the University of Saskatchewan.
The National Institutes of Health provided funding for the research.
========================================================================== Story Source: Materials provided by Oregon_State_University. Original
written by Steve Lundeberg. Note: Content may be edited for style
and length.
========================================================================== Journal Reference:
1. Ross M. Warner, Robyn Shuttleworth, James D. Benson, Ali Eroglu,
Adam Z.
Higgins. General tissue mass transfer model for
cryopreservation applications. Biophysical Journal, 2021; DOI:
10.1016/j.bpj.2021.10.014 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2021/11/211110104641.htm
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