Writer｜Katherine Yang
Layout Designer｜Cecilia Qin
Organ Preservation
A new breakthrough in organ preservation, safe transplantation is not a dream!
Most people must hear about transplant surgery before. Commonly known organ transplants include the liver, kidney, and cornea. However, contemporary transplant procedures frequently encounter two significant challenges. First, the demand for organs is far greater than the amount of donations. In addition to the crime problems arising from the imbalance between supply and demand, it is also necessary to compare the degree of fit between the donor and the patient. The second problem is that organ preservation could be better. The importance of organ preservation is not only because of the need for organ transfer but also because the operation cannot be completed in a short period of time, so maintaining the activity of organs during this period is also extremely important. So today we will introduce to you the development of organ transplantation and organ preservation.
Introduction to Organ Transplatation
In a comprehensive context, organ transplantation can be classified into two primary categories: organs and tissues. The category of organs encompasses vital structures such as the heart, lungs, kidneys, liver, pancreas, and small intestine. On the other hand, tissues consist of diverse elements such as solid bones, cartilage, ligaments, tendons, corneas, amniotic membranes, blood vessels, heart valves, peripheral blood stem cells, umbilical cord blood, skin, and bone marrow.
Organ transplants can be further categorized based on their sources into two primary types: living donor organ donation transplants and cadaveric organ donation transplants.
Living organ donation and transplantation pertain to the act of a healthy adult voluntarily offering a portion of their own organs or tissues for transplantation, without compromising their own overall health and physiological functions. Among these cases, liver and kidney donations are the most prevalent.
In the case of organ donation and transplantation from cadavers, the process involves obtaining consent for organ donation from the deceased individual prior to their passing. Subsequently, the organs are retrieved after the donor has been declared brain-dead or has passed away. It's important to highlight that in numerous countries, the sources of "legitimate" organs are procured without financial transactions.
Organ Preservation
Moving forward, let us delve into the central theme of this article - organ preservation. The pivotal prerequisite for the triumphant accomplishment of organ transplantation lies in the imperative need to sustain the viability of the organ. This viability must be maintained starting from the moment the organ is detached from the donor until the primary blood vessels are interconnected with the recipient. Within this critical interval, any loss of organ functionality is irreversible and leads to a forfeiture of its initial purpose.
To illustrate, let's consider the cases of kidney and liver. Following the cessation of their blood supply, these organs face deprivation of essential oxygen and nutrients. Once outside the body, kidneys can sustain their functionality for a duration of 45 to 60 minutes at room temperature. On the other hand, the liver's capability to retain its activity is confined to a mere 10 to 15 minutes.
Therefore, in clinical practice, the shorter the ischemic time of an organ, the better. However, this time is extremely limited, and doctors barely have enough time to complete the surgery. As a result, humans have been continuously working to extend organ viability. Currently, there are two methods used in clinical practice to achieve this goal. Firstly, organs are either immersed in an organ preservation solution or continuously perfused with such a solution. This method primarily relies on the organ preservation solution to provide the minimum required nutrients for maintaining cellular viability and protecting the cells. Secondly, low-temperature preservation is utilized to reduce cellular metabolism. Current techniques often combine both methods in application, but they are researched separately in the scientific field. Therefore, the following discussion will also be divided into two parts: organ preservation solutions and organ preservation techniques.
Organ Preservation Solution
The concept of "organ preservation solution" first emerged in the manuscript of the French internist César Julien Jean Legallois in the year 1812. He boldly hypothesized that the injection of fluids could sustain the activity of the heart. With this, he officially initiated the beginning of organ preservation techniques.
Initially, there was an idea to utilize blood from the same species to maintain organ activity. However, this concept proved entirely impractical for human application due to the large demand for blood. Consequently, scientists embarked on further research to explore the possibility of using blood from species A to sustain the organs of species B. However, the results unveiled that cross-species blood infusion was toxic and led to a rapid deterioration of the organs.
Currently, the organ preservation solutions available in the market can primarily be categorized into three types: intracellular fluid (ICF)-type solutions, extracellular fluid (ECF)-type solutions, and amino acid-type solutions.
ICF-type solutions
Compared to other types of preservation solutions, ICF-type solutions mainly consist of low Na+ and high K+ concentrations. The first ICF-type solutions was the Collins solution, developed by Collins and colleagues in 1969. This marked the world's first cell preservation solution. However, the Collins solution had a significant drawback: the presence of magnesium phosphate precipitates, which could lead to crystal residues in the kidneys, adversely affecting renal function. To address this concern, a team modified the Collins solution in 1980, giving rise to the Euro-Collins solution, which has been in use since. Shortly after, the University of Wisconsin solution, with similarly low sodium and high potassium content, was introduced and is also still in use today.
ECF-type solutions
Differing from intracellular preservation solutions, extracellular preservation solutions primarily consist of low potassium and high sodium compositions. The most common examples of these solutions include EP4 (or EP-TU) solution, LPDG solution, and ET-K solution.
Amino acid-type solutions
In addition to the ICF-type solutions or ECF-type solutions, this category of solutions incorporates amino acids and histidine buffer systems. This addition has also proven to yield favorable preservation outcomes. Common examples of amino acid preservation solutions include HTK solution, Custodiol-N solution, and Celsior solution.
In addition to the three categories of organ preservation solutions mentioned above, numerous biotechnology companies are continually researching solutions with different compositions. For instance, Renfang (Beijing) Biomedical Research Institute Co., Ltd. has developed a novel oxygen-carrying organ preservation solution. This solution employs hemoglobin, a biomaterial known for its efficient oxygen-carrying capabilities, as a key component. This technology has already obtained a patent in China and demonstrates the potential to significantly enhance organ utilization rates, surgical success rates, and patient survival rates.
Organ Preservation Technology
Currently, the most prevalent organ preservation technique is cold storage, where for every 10°C decrease in temperature, the metabolic rate decreases by a factor of two. While cold storage is the most cost-effective preservation method, it presents potential challenges such as the formation of ice crystals within the organs and the possibility of uneven cooling, both of which can lead to organ damage.
Apart from cold storage techniques, there is ongoing research into the vitrification freezing technique. Vitrification freezing employs highly concentrated cryoprotectants to dehydrate cells, followed by rapid cooling, preventing the formation of ice crystals within the cytoplasm. This technique has been applied to embryo freezing, but its application to organs still faces certain challenges. For instance, cryoprotectants in sufficient doses are toxic and can induce additional cell damage, so determining the appropriate dosage remains a subject of investigation. Additionally, uneven thawing rates can also harm organs.
However, addressing the latter concern, a new solution was presented in the June issue of "Nature" this year - nanowarming. This technique successfully thawed a mouse kidney that had been frozen for 100 days, and the kidney exhibited good post-thaw condition, successfully enabling transplantation.
The last technique to be introduced is the commercially available normothermic preservation. In 2008, a research team from the University of Oxford established the OrganOx Medical company, which sought to closely replicate the in vivo environment, including factors such as temperature, blood perfusion rates, and pulsatile blood pressure. This technique has been adopted for clinical use in the United States; however, the device's cost is considerably high, and its usage requires the agreement to provide organ data to the research team, contributing to its relatively low market adoption.
Beyond the University of Oxford team, another group from Switzerland has been researching normothermic preservation techniques. They published their results in May of last year in "Nature." This Swiss team comprises professionals from the engineering, biochemistry, and medical fields. Notably, the donor, in this case, had a history of abdominal desmoid fibromatosis and had suffered from long-term infection and sepsis. Such organs with such medical histories are generally not considered for donation. Nonetheless, the research team preserved the organ in the device for three days while simultaneously administering antibiotic treatment. Ultimately, they successfully restored the organ's health and performed a successful transplantation, highlighting the advantages of normothermic preservation.
Conclusion
Currently, there exists a severe global imbalance between the supply and demand of organs, with this issue being particularly pronounced in Eastern societies. The primary cause stems from the belief in Eastern cultures that post-death preservation of bodily integrity is essential. However, in practice, whether it's through living or deceased donation, surgeries are conducted to the standards of surgical procedures. In cases of deceased donation, substitutes are employed to fill and suture, restoring the appearance, and making it indistinguishable from standard surgical procedures.
Overall, it’s important to emphasize that as scientists diligently work on developing these technologies, more sustainable organs can be left in the world and more lives can be saved.
Комментарии