Beating heart tissue supercooled and revived for the first time
A major challenge when it comes to preserving tissues and organs for transplantation is preventing the buildup of ice crystals that can cause critical damage, but an emerging technology may help sidestep the whole issue. Scientists have used a promising supercooling technique to preserve and revive engineered heart tissue for the first time, hinting at a future where donated organs may remain viable for far longer periods of time.
The technology at the center of this breakthrough is called isochoric supercooling and was pioneered by Boris Rubinsky at the University of California, Berkeley around 16 years ago. The technique seeks to avoid the formation of harmful ice crystals during preservation of biological material, and is also starting to show promise in food preservation, where it could lead to massive energy savings according to research published earlier this month.
Where conventional isobaric freezing exposes material to an atmosphere at constant pressure to freeze it solid, isochoric freezing submerges the material in a liquid. It is then sealed away in an air-free, rigid container, where there is no space for the ice crystals to form, even when temperatures are cooled to below freezing. Rubinksy's team has previously cooled samples to as low as -22 °C (-7 °F) and left 40 percent of the material unfrozen.
“This is fundamental thermodynamics," Rubinksy says. "When the material to be frozen is confined in a rigid box, then only part of the volume freezes."
In their latest experiments, the researchers used a previously developed heart-on-a-chip system, where cardiac tissue is grown from adult stem cells. This tissue beats at a similar rhythm to a human heart, and microfluidic channels are used to simulate the exposure of the cells to nutrients and drugs. This engineered tissue was submerged in an isochoric supercooling chamber and chilled to -3 °C (26.6 °F), with heart cells then removed at 24, 48 and 72 hours and returned to a warm 37 °C (98.6 °F).
Spontaneous beating resumed for between 65 to 80 percent of the samples, with no significant difference observed between those cooled for the different durations. Inspection of the samples showed the ischoric supercooling had not changed the structural integrity of the heart tissue, or greatly altered the beat rate or waveform, though there was a slight upward trend in the heartbeat duration of the tissue cooled for longer periods. The tissue also remained responsive to medication called isoproterenol, used to increase heart rate.
“To our knowledge, this is the first-ever report of the supercooling and revival of an autonomously beating, engineered human cardiac muscle,” said study co-lead author Matt Powell-Palm, a postdoctoral scholar in Rubinsky’s lab.
Successfully reviving the heart tissue after preserving it in a supercooled state for one to three days is a promising proof-of-concept for the technology. It could help greatly expand the window of time donated hearts remain viable for, which is currently measured only in hours and significantly limits access to patients in need.
“Currently, patients in Florida cannot receive a heart or lung from California because the organ would not survive the cross-country trip,” said Powell-Palm.
The scientists hold a patent for the technology and are working on ways to translate it for clinical use, work that includes scaling it up to tackle entire organs.
“The technology used to cool the tissue is sound and robust, but we now need to develop techniques to warm things up consistently,” said study author Kevin E. Healy. “That was easier with the mini heart muscles we used for this study. Working on whole organs will require more work.”
The research was published in the journal Communications Biology.