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The long and winding road to immune tolerance
No matter how many new immunosuppressive medications reach the market, the “Holy Grail” of transplantation has always been (and according to some will continue to “always” be) the induction of donor-specific immunologic tolerance. In this effort to modulate the immune system, there have been a multitude of different approaches and candidates at the cellular or molecular level. Dendritic cells (DC), as possibly the most effective antigen presenting cells, appear to play a critical role in moderating the immune response.Genomics and transplantation: a brave new world is (almost) here
The era that we live in appears to be one that is dominated by genomic medicine, as the amount of genomic data has increased exponentially over the last several years, thus providing specific targets at the gene level for intervention in a variety of pathophysiological processes [1,2]. This has led to a shift in how we approach different biological mechanisms, as the challenge of understanding the human genome offers the possibility of a personalized approach to the individual patient with the unique genomic data.Commentary on “Combined treatment with regulatory T cells and vascularized bone marrow transplantation creates mixed chimerism and donor-specific tolerance to vascularized composite allografts without cytoreductive conditioning”
Transplantation of vascularized composite allografts (VCAs) could significantly affect the liver of the approximately 7 million Americans every year. These Americans would benefit from transplantation because they had undergone or need to undergo reconstructive surgery as the result of oncologic procedures, congenital anomalies, and trauma [1]. Just as important, it may also help bring us a step closer to the “Holy Grail” of transplantation, which is the induction of donor-specific immunologic tolerance.Commentary on: Lipid peroxidation in machine perfusion of older donor kidneys
It is a universally accepted fact that kidney transplantation improves quality of life and patient survival in patients with end-stage renal disease [1]. However, the success of renal transplantation has generated its biggest challenge, which is none other than the growing disparity between available organs on the one hand and the increasing need on the other hand. According to data from the United Network for Organ Sharing (UNOS), the annual increase of patients on the transplant waiting list is approximately five times the number of transplantation procedures, leading to a 6% mortality rate for patients on the waiting list for a renal transplant [2,3].Commentary on: Age-related differences in hepatic ischemia/reperfusion: gene activation, liver injury, and protective effect of melatonin
Ischemia/reperfusion (I/R) injury represents a process of blood deprivation during the ischemia period followed by the release of a high number of a variety of mediators during the reperfusion period, which can potentially lead to cellular and, eventually, organ dysfunction. This basic mechanism is critical in a variety of different fields of surgery, including trauma, vascular, and transplantation surgery, with the liver being one of the organs most frequently involved. Finding ways to ameliorate the I/R injury observed in liver transplantation or resection can go a long way towards improving their respective results, as well as towards increasing the number of transplants by being able to improve the quality of available hepatic grafts.Commentary on “Optimizing chimerism level through bone marrow transplantation and irradiation to induce long-term tolerance to composite tissue allotransplantation”
What started as a noble undertaking in the 4th century AD by the twin saints Kosmas and Damian developed into a quest for the Holy Grail of transplantation. The two saints, according to the legends, grafted a lower extremity from a recently deceased Ethiopian to replace the ulcerated leg of a patient [1]. That was an early beginning of the concept of composite tissue allotransplantation (CTA), whose realization brought together a variety of different surgical specialties, with plastic and reconstructive surgeons at the forefront.Commentary on “Interaction between Kupffer cells and platelets in the early period of hepatic ischemia-reperfusion injury”
Ischemia/reperfusion (I/R) injury represents an extremely active field of basic science research. The reason is that it involves a complex series of events with multiple protagonists (which have not been well defined yet), as well as the fact that it is an event common in a variety of clinical situations, including transplantation, liver resection, trauma, and vascular surgery. The basic mechanism is that of the sequence of ischemia, followed by the return of blood flow, with the reperfusion causing the activation of inflammatory cascades.Blockade of chloride ion transport enhances the cytocidal effect of hypotonic solution in gastric cancer cells
Since 1905, intraoperative peritoneal lavage has been widely performed to remove bacteria and tumor cells from the abdominal cavity [1]. Cells released from serosally invasive tumors, or even from patients with early stage tumors, can lead to peritoneal recurrence and metastasis [2]. In the case of the early stage tumors, surgical manipulation and lymphatic drainage can play a critical role in peritoneal metastasis. Although this pattern has been observed over time in different types of cancer, it has been more prominent in gastric cancer [3,4].Commentary on “Preemptive Therapy with Steroids but not Macrolides Improves Gas Exchange in Caustic-Injured Donor Lungs”
Lung transplantation has become a well-accepted treatment for patients with end-stage pulmonary disease [1]. An important rate-limiting step in covering the needs of the continuously growing number of patients on the waiting list is a shortage of donor lungs. From the large number of donor lungs offered for transplantation, only about 15%–20% meet the existing inclusion criteria [2]. The result is that 20%–30% of patients die while awaiting lung transplantation [3]. Some of the reasons leading to exclusion of potential grafts are tobacco use, barotrauma, pneumonias, or aspiration-associated injury among others.Cyclosporin-A Does Not Prevent Cold Ischemia/Reperfusion Injury of Rat Livers
Ischemia/reperfusion (I/R) injury is one of the more fascinating topics in basic science, as it involves a complex series of events that ultimately lead to cellular and tissue damage. The basic mechanism is one of blood deprivation during ischemia, followed by the return of flow during reperfusion, with the release of a variety of different mediators that can cause cellular and organ dysfunction. The value and intrigue of I/R injury is, to an extent, due to the following two reasons. The first is that it involves a great number of variable pathways, which in several cases interact with each other, thus leading to a high number of candidates for potential therapeutic intervention.
