CC BY
4DOI 10.24412/cl-37136-2023-1-35-38
OPTICAL TECHNOLOGIES FOR ORGAN TRANSPLANTATION PROCEDURES
JOSÉ VOLLET-FILHO1 , LORAINE GOENAGA-MAFUD1 , YORDANIA GÂMEZ1 , SOFIA SANTOS12 , NATALIA INADA1 , ORLANDO CASTRO-E-SILVA3 , CRISTINA KURACHI1 , AND
VANDERLEI BAGNATO1,4
1Sao Carlos Institute of Physics, University of Sao Paulo, Brazil2 Institute of Geosciences and Exact Sciences, Sao Paulo State University "Julio de Mesquita Filho", Brazil 3Ribeirao Preto Medical School, University of Sao Paulo, Brazil 4Department of Biomedical Engineering, Texas A&M University, United States
volletfilho@usp.br
TRANSPLANTATION PROCEDURES
Transplantation is a surgical procedure that is effective in treating advanced-stage organ failure. It involves replacing a dysfunctional organ or tissue of a recipient with a compatible organ or tissue from a live or deceased donor. Its main objective is to restore organ functionality and ensure the survival of the recipient. There are two types of transplant: living donor transplant and deceased donor transplant. Living donor transplant is only possible for certain organs, such as the kidney, liver, lung, and bone marrow. According to the law, only relatives up to the fourth degree and spouses can be donors in this case. Non-relatives can donate only with judicial authorization. Deceased donor transplant is considered only when the donor has been diagnosed with brain death, and the target organ to be donated is physiologically normal, in addition to having the consent of the family and the recipient. Solid organ transplantation is the preferred treatment for improving the quality of life of people with irreversible chronic diseases that affect organs such as the kidney, pancreas, liver, heart, and lungs. The demand for solid organ transplants is growing rapidly worldwide due to the increase in diseases that cause terminal organ failure, such as terminal heart failure, chronic obstructive pulmonary disease, chronic liver cirrhosis and fibrosis, hepatic encephalopathy, hemorrhagic esophageal varices, acute liver failure, hepatitis/fulminant necrosis, and malignant diseases such as hepatocellular carcinoma, hepatoblastoma, hemangioendothelioma, cholangiocarcinoma, non-alcoholic steatohepatitis (NASH), alcoholic cirrhosis, hepatitis C, chronic renal failure, glomerulonephritis, polycystic kidney disease, congenital malformations, and lupus, among others. In these cases, organ transplantation may be the only treatment option for the patient's survival [1-5]. In 2019, 153,863 solid organs were transplanted globally, including kidneys, livers, hearts, lungs, pancreases, and intestines, but this only represents approximately 10% of the global demand, according to the Global Observatory on Donation and Transplantation (GODT). In Brazil, as of December 2020, there were 43,642 patients on the waiting list for organ transplantation, with the highest number of registered patients in Sâo Paulo [6, 7]. Ex vivo perfusion is used for dynamic preservation of different solid organs, allowing continuous evaluation of transplant viability and the preservation of marginal organs. This technique expands the donor pool, reduces the risk of primary non-function, and extends the safe preservation period. However, organ transplantation is still challenging due to long waiting lists, infections, incompatibility between donor and recipient, and organ availability, which is a major limitation leading to an increased mortality rate of patients on the waiting list. To expand the number of organs available for transplantation, many transplant programs have expanded their donor acceptance criteria, including the use of marginal or borderline grafts [6, 7]. Optical techniques are promising regarding its use to investigate, monitor and enhance transplantation organ procedures, as both monitoring and therapeutical procedures can be improved by using light as a tool. Here, we present some of the possible approaches under development with contribution of our research group: assessment tools involving fluorescence spectroscopy for transplanted organs and therapeutical/preparing optical procedures for the enhancement or enabling of organ grafts for transplantation [8].
FLUORESCENCE SPECTROSCOPY FOR TRANSPLANTATION ASSESSMENT AND MONITORING
Fluorescence emission of biomolecules, both endogenous and exogenous, is a widely used technique in biophotonics for diagnosis and therapy. This is due to the characteristic emissions in visible and near-infrared ranges of the electromagnetic spectrum. Fluorescence is a phenomenon where light emission is obtained from electronic state transitions between an excited state and a more fundamental state of the same spin. This is observed in a variety of biological molecules, including human tissue molecules and photosensitizers. Fluorescence techniques depend on the concentration and characteristics of the electronic state available in molecules, which depend on their constitution, structure, and environment. Therefore, information that identifies biological molecules and tissues can be obtained through fluorescence, allowing for the detection and monitoring of specific biological processes. Fluorescence spectroscopy is a specific technique regarding spectral resolution, allowing for the identification of fluorescent molecules and changes in tissue characteristics. It has been used for decades in the monitoring of tissue characteristics and changes. Differently from fluorescence imaging, which allows for wider applications as it enables wide-field and microscopy detection, fluorescence spectroscopy increases the spectral resolution of information. Spectroscopy has been investigated as a tool to identify lesions using endogenous fluorescence differences or exogenous biomarkers. It can also monitor biological processes such as photosensitizers' pharmacokinetics, which involves monitoring their distribution, accumulation, and clearance at cells and tissues over time. Spectroscopy demands the use of lasers for excitation and optical fibers to deliver light and collect fluorescence, making it limited as a point-by-point detection but increasing the resolution of spectral information [9-14]. Since fluorescence spectroscopy can be utilized to identify tissues based on their characteristic spectra, it thus allows determining whether organ grafts are suitable for transplantation or to which extent changes they undergo during a transplantation procedure can be tolerated for viable organs. This approach is currently under development and is based on the principle that the optical properties of viable biological tissues depend on their molecular composition, concentration, and tissue structure. Any abnormalities that may arise in the tissue will produce differences in optical characteristics such as fluorescence emission and light propagation. By identifying patterns of normality or abnormality in tissues classified by accepted clinical standards (Fig. 1), an effective method can be provided for the detection of organ issues that might predict complications leading to death after transplantation. This approach can help surgeons make judgments on organ grafts with borderline acceptability, and greatly contribute to clinical practice. It has been shown that changes in the intensity and/or shape of fluorescence emission bands can be correlated to the preservation solution perfusion and blood reperfusion during liver transplantation procedures, where any complication may lead to an inefficient preservation of the graft and thus severe risk to transplanted patients [15-18].
Figure 1: Fluorescence spectra and variation of standards. (a) Fluorescence spectra at 408 nm excitation for different transplant stages (AF = autofluorescence; BT = backtable; WR60 = 60 min after warm reperfusion). (b) Example of abnormality offluorescence ratios in spectra for non-surviving patients - spectral profile changes, indicating degeneration
in the organ (adaptedfrom [16]).
OPTICAL TECHNIQUES FOR MICROBIOLOGICAL CONTROL IN TRANSPLANTATION ORGANS
The colonization or infection by microorganisms presents another challenge for organ transplantation, and potentially infected donor organs are usually discarded, further decreasing the available number of organs for transplantation. Thus, another promising approach of optical techniques for transplants involves their use to reduce the microbiological load of microorganisms in organs that would otherwise be eligible for transplantation [6, 19-22]. Microbiological contamination is often found in patients with severe morbidities, and organs are usually discarded for donation. The emergence of antimicrobial resistance and multi-drug resistant (MDR) microorganisms, especially in hospital settings, highlights the need for alternative methods to antibiotic use for decontaminating organs. Microorganisms of concern for antimicrobial resistance include methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), Klebsiella pneumoniae carbapenemase (KPC), NDM-1, MDR-TB (multidrug resistant tuberculosis), Actinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus faecium, and Proteus sp. However, the development of new generations of antibiotics to combat these superbugs is unlikely in the near future. Therefore, reducing the indiscriminate use of antibiotics and exploring alternative treatments is crucial. Ultraviolet C irradiation (UV-C) showed to be an alternative with microbiological reduction effects that can inactivate microorganisms without the use of chemicals. With the appropriate fluence and wavelength (commonly centered circa 254 nm), UV-C can dimmerize DNA and disrupt nucleic molecules of the target, preventing them from reproducing, and directly inactivate them by destroying their cell walls and membranes. The high photon energy of UV-C can damage all biomolecules, particularly lipids, proteins, and nucleic acids, leading to non-specific biological target action. UV-C has shown effectiveness in water treatment, food and surface disinfection, and can be a promising method for decontaminating organs [23-38]. An initiative has recently shown that lung transplantation could be greatly benefited by decontaminating the preservation solution during ongoing circulation through the organ with UV irradiation prior to the procedure. This approach reduced the microbiological load of the organ and contributed to better quality results of the procedure. Currently, the same approach is being investigated for kidney and liver transplantation using similar processes, both with UV irradiation and proposing a photodynamic inactivation approach [39]. Combining ex vivo organ perfusion with ultraviolet C radiation (Fig. 2) may therefore provide an alternative treatment for contaminated grafts. The perfusate is directly irradiated with UV-C, which eliminates the microbial load without damaging the organ itself. Studies have shown that ex vivo organ perfusion improves graft metabolic conditions and transplant success. Our group recently reported on the development of an ex vivo lung and kidney perfusion machine, which includes a UV-C irradiation protocol. Another option of optical technique for this approach is exploring photodynamic effects in microbiological control (namely photodynamic inctivation or PDI). PDI involves using a photosensitizer (PS) that generates reactive oxygen species (ROS) when activated by light at a specific wavelength and in the presence of oxygen. It has been successful in destroying tumor cells and treating microbial infections. PDI offers advantages over uv-C, particularly by providing a technique that do not demand ultraviolet radiation, thus offering lower light absorption by non-targeted structures and thus avoiding undesired damage to tissue [40].
Figure 2: UV-C decontamination of circulating perfusate - proo-of-principle. (a) UV-C irradiation device, with quartz tube among UV-C lamps, irradiating the circulating solution. (b) Representation of the decontamination process - preservation solution is perfused through the organ, and irradiated externally by UV-C light.
(a)
(b)
PHOTOBIOMODULATION FOR THE IMPROVEMENT OF PROCEDURES
Optical techniques have not only been investigated for clinical approaches to transplantation procedures but also for phototherapeutic techniques. Recent studies have explored whether phototherapy protocols can aid in the preservation and maintenance of organ grafts before, during, and/or after transplantation. Promising results were observed in rat livers where the administration of 660 nm laser irradiation protocols prevented certain aspects of lesions caused by ischemia and blood reperfusion. These findings suggest that specific light delivery to organs undergoing transplantation can offer significant protection and may improve transplantation outcomes [41-43].
REFERENCES
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[4] Rudow, D. L., Goldstein, M. J. Critical care management of the liver transplant recipient. Critical Care Nursing Quarterly, v. 31, n. 3, p. 232-243, 2008.
[5] Kwong, A. J., Fix, O. K. Update on the management of liver transplant patient. Current Opinion in Gastroenterology, v. 31, p. 224-232, 2015. DOI:10.1097/MOG.0000000000000173.
[6] World Health Organization. Activities global observatory on Donation & Transplantation. 2019. Available at: . Acess on: Jul. 3, 2021.
[7] Associaçâo Brasileira de Transplante de Orgâos. Dimensionamento dos transplantes no Brasil e em cada estado (2013-2020). Registro Brasileiro de Transplantes, v. 26, n. 4, p. 1-88, 2020.
