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A new technique for decontaminating organs before transplantation using UV and red light irradiation has been developed by researchers at the São Paulo Research Foundation (FAPESP) in partnership with the University of Toronto. The biophotonic decontamination technique, which was initially developed to decontaminate lungs with viral infections such as hepatitis C, could help prevent transmission of diseases to organ recipients and increase the number of transplants.
The technique consists of two procedures performed concurrently. During perfusion — a procedure for decontaminating lungs before transplantation by replacing the blood with a preservation liquid — the organ to be transplanted is irradiated with red light with a wavelength of 660 nm until photodynamic oxidation eliminates the microorganisms in the tissue. At the same time, the viral load is flushed away by the circulating liquid, which is continuously decontaminated by UV irradiation with a wavelength of 254 nm.
A photosensitizing drug is introduced into the perfusion liquid. Activation of the drug requires oxygen molecules (present in viruses) and red light irradiation at 660 nm. When the photosensitizing drug is bathed in red light, its molecules absorb energy, which is transferred to the oxygen molecules in the virus, making them highly oxidized. This causes irreversible damage to the membranes and genetic material of several viruses, including hepatitis C virus and HIV-1.
“The ultraviolet irradiation directly destroys microorganisms by breaking down the molecules present in bacteria and viruses,” professor Cristina Kurachi said. “The bacteria are killed, and the viruses are completely inactivated. Red light irradiation decontaminates indirectly via photosensitization.”
The perfusion solution used for the procedure is expensive, and because of its cost, as little as possible is used in the procedure. “Thanks to the technique and equipment we’ve developed, a liter of the perfusate can be flushed through the organ hundreds of times to remove the contaminants completely,” said professor Vanderlei Bagnato.
Pig lung being irradiated with red light to inactivate viruses. Method developed by scientists in Brazil and Canada can prevent transmission of diseases to organ recipients. Courtesy of Cristina Kurachi.
The method was first tested on human lungs rejected for transplantation to determine whether the tissue viral load could be reduced by irradiation. According to thoracic surgeon Marcelo Cypel, who heads the lung transplant program at the University of Toronto and developed the perfusion procedure, the viral load was significantly lower after the procedure. The technique was further tested on pig lungs and on patients.
“In the first 10 transplants we performed, the new technique eliminated hepatitis C virus from organs donated to two patients,” Cypel said. “In the other eight patients, viral load fell sharply after surgery but rose again seven days later, and the patients had to be given antiviral treatment for three months.”
The researchers plan to refine the biophotonic therapy to assure even sharper reductions in the viral and bacterial loads, increasing the chances of successful transplants. “Our aim is to have light-based therapy eliminate all viral and bacterial contaminants in organs to be transplanted,” Bagnato said. “If so, it may even be possible to do without the perfusate.”
According to Bagnato, the technique was initially developed to treat lungs but is being adapted for livers and kidneys. “This should greatly improve postoperative conditions for transplant recipients,” he said. “It will also enable us to use organs that we must currently reject because of the level of contamination.”
A patent application has been filed in Canada, and two multinationals have expressed an interest in studying the possibility of producing and marketing the light therapy equipment. The researchers are now working on the implementation of a liver and kidney decontamination program in Brazil.
The research was published in Nature Communications (https://doi.org/10.1038/s41467-018-08261-z).READ MORE