Allotransplantation

Balancing the immune response after solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA) remains an ongoing clinical challenge. While immunosuppressants can effectively reduce acute rejection rates following transplant surgery, some patients still experience recurrent acute rejection episodes, which in turn may progress to chronic rejection. Furthermore, these immunosuppressive regimens are associated with an increased risk of malignancies and metabolic disorders. Despite significant advancements in the field, these IS related side effects persist as clinical hurdles, emphasizing the need for innovative therapeutic strategies to improve transplant survival and longevity...

Antibody-mediated rejection (AMR) is a common cause of graft failure after pig-to-nonhuman primate organ transplantation, even when the graft is from a pig with multiple genetic modifications. The specific factors that initiate AMR are often uncertain. We report two cases of pig kidney transplantation into immunosuppressed baboons in which we identify novel factors associated with the initiation of AMR. In the first, membranous nephropathy was the initiating factor that was then associated with the apparent loss of the therapeutic anti-CD154 monoclonal antibody in the urine when severe proteinuria was present...

The major role of CD8+ T cells in clinical and experimental transplantation is well documented and acknowledged. Nevertheless, the precise impact of CD8+ T cells on graft tissue injury is not completely understood, thus impeding the development of specific treatment strategies. The goal of this overview is to consider the biology and functions of CD8+ T cells in the context of experimental and clinical allotransplantation, with special emphasis on how this cell subset is affected by currently available and emerging therapies...

Facial transplantations have become a clinical reality as the last reconstructive option in severely disfigured patients. To date, clinical outcomes remain unclear. The purpose of this paper was to analyse the outcomes in facial transplantation (FT) and determine the risks and benefits of FT based on short- and long-term outcomes. An electronic literature search was performed across PubMed, EMBASE and the Cochrane Central Register for Controlled Trials (CENTRAL) databases to capture all the relevant records relating to outcomes in FTs from 2005 to 2021...

Regulatory T cells (Tregs) play a crucial role in the homeostasis of the immune response. Tregs are mainly generated in the thymus and are characterized by the expression of Foxp3, which is considered the Treg master transcription factor. In addition, Tregs can be induced from naïve CD4+ T cells to express Foxp3 under specific conditions both in vivo (pTregs) and in vitro (iTregs). Both subsets tTregs and pTregs are necessary for the establishment of immune tolerance to self and non-self antigens. Although it has been postulated that iTregs may be less stable compared to tTregs, mainly due to epigenetic differences, accumulating evidence in animal models shows that iTregs are stable in vivo and could be used for the treatment of inflammatory disorders including autoimmune diseases and allogeneic transplant rejection...

BACKGROUND: Pancreas transplant volumes are limited because of poor utilization of "extended criteria grafts." Prolonged cold ischemia is a risk factor associated with poor allograft survival. We aimed to establish the feasibility of transplantation using grafts subjected to prolonged cold ischemia and determine whether these grafts could be optimized using normothermic ex vivo perfusion (NEVP) in a porcine model. METHODS: The study population consisted of 35 to 40 kg male Yorkshire pigs in an allotransplantation model with a 3-d survival plan for recipients...

BACKGROUND: Allograft rejection remains a major obstacle to long-term graft survival. Although previous studies have demonstrated that IL-37 exhibited significant immunomodulatory effects in various diseases, research on its role in solid organ transplantation has not been fully elucidated. In this study, the therapeutic effect of recombinant human IL-37 (rhIL-37) was evaluated in a mouse cardiac allotransplantation model. METHODS: The C57BL/6 recipients mouse receiving BALB/c donor hearts were treated with rhIL-37...

The field of transplantation, including the specialized area of vascularized composite allotransplantation (VCA), has been transformed since the first hand transplant in 1998. The major challenge in VCA comes from the need for life-long immunosuppressive therapy due to its non-vital nature and a high rate of systemic complications. Ongoing research is focused on immunosuppressive therapeutic strategies to avoid toxicity and promote donor-specific tolerance. This includes studying the balance between tolerance and effector mechanisms in immune modulation, particularly the role of costimulatory signals in T lymphocyte activation...

Overcoming immunological rejection remains a barrier to the safe adoption of Vascularised Composite Allotransplantation (VCA). To mitigate this risk, clinical protocols have been derived from solid organ transplantation, targeting recipient immunomodulation, yet VCA is unique. Face and hand composite allografts are composed of multiple different tissues, each with their own immunological properties. Experimental work suggests that allografts carry variable numbers and populations of donor leukocytes in an organ specific manner...

Face transplant (FT) has emerged as a groundbreaking option for patients with severe facial deformities, resulting from congenital disorders, trauma, or tumor ablation. Although reconstructive surgery has made significant strides, the challenges of restoring both form and function remain, particularly in centrally located defects. This review explored the long-term outcomes of FT, addressing its challenges and potential pitfalls. A systematic review following the PRISMA guidelines was conducted, encompassing articles published in English from November 2005 to January 2023, which were searched across PubMed, MEDLINE, and EMBASE databases...

IMPORTANCE: Posthumous whole-eye (globe) donations for research lack a mechanism that reinvolves the existing ophthalmic research team of the donor unless there is a preplanned donor directive. Disconnection between the deceased and their research team equates to lost opportunities for the research team to have a longitudinal view of the eyes that have been involved in their research. OBJECTIVES: To use the clinical trial informed consent process to create a posthumous research donation opportunity that directs the donation to the currently affiliated research team of the donors (preserving the longitudinal research experience)...

OBJECTIVES: Vascularized composite allotransplantation is a reconstructive option after severe injury but is fraught with complications, including transplant rejection due to major histocompatibility complex mismatch in the context of allogeneic transplant, which in turn is due to altered immuno-inflammation secondary to transplant. The immunosuppressant tacrolimus can prevent rejection. Because tacrolimus is metabolized predominantly by the gut, this immunosuppressant alters the gut microbiome in multiple ways, thereby possibly affecting immunoinflammation...

Due to organ donor shortages, long transplant waitlists, and the complications/limitations associated with auto and allotransplantation, biomaterials and tissue-engineered models are gaining attention as feasible alternatives for replacing and reconstructing damaged organs and tissues. Among various tissue engineering applications, bone tissue engineering has become a promising strategy to replace or repair damaged bone. We aimed to provide an overview of bioactive ceramic scaffolds in bone tissue engineering, focusing on angiogenesis and the effect of different biofunctionalization strategies...

An estimated 1.5 million Americans suffer from Type I diabetes mellitus, and its incidence is increasing worldwide. Islet allotransplantation offers a treatment, but the availability of deceased human donor pancreases is limited. The transplantation of islets from gene-edited pigs, if successful, would resolve this problem. Pigs are now available in which the expression of the three known xenoantigens against which humans have natural (preformed) antibodies has been deleted, and in which several human 'protective' genes have been introduced...

Chronic kidney disease affects an estimated 37 million people in the United States; of these, >800,000 have end-stage renal disease requiring chronic dialysis or a kidney transplant to survive. Despite efforts to increase the donor kidney supply, approximately 100,000 people are registered on the kidney transplant waitlist with no measurable decrease over the past 2 decades. Outcomes of kidney transplantation are significantly better than for chronic dialysis: kidney transplant recipients have lower rates of mortality and cardiovascular events and better quality of life, but waitlist time matters...

BACKGROUND: Apart from the skin, little is known about the immunological processes in deeper tissues, which are typically not accessible to biopsy and inspection, of vascularized composite allografts (VCAs). Face transplant patients develop prominent adenopathy shortly after transplantation that resolves over time. The mechanisms underlying this process are not understood. MATERIALS AND METHODS: A retrospective cohort study was conducted on 9 patients who underwent 10 facial VCAs at the Brigham and Women's Hospital, Boston, MA, between April 2009 and July 2019...

For children with complex congenital heart problems, cardiac allotransplantation is sometimes the best therapeutic option. However, availability of hearts for pediatric patients is limited, resulting in a long and growing waitlist, and a high mortality rate while waiting. Cardiac xenotransplantation has been proposed as one therapeutic alternative for neonates and infants, either in lieu of allotransplantation or as a bridge until an allograft becomes available. Scientific and clinical developments in xenotransplantation appear likely to permit cardiac xenotransplantation clinical trials in adults in the coming years...

BACKGROUND: The lack of noninvasive biomarkers for graft rejection remains a challenge for the accurate monitoring of vascularized composite allotransplants. Viral vector-mediated gene transfer is a promising method for preventing graft rejection. In this study, we aimed to establish the expression profile of microRNAs (miRNAs) in skin flap allotransplantation, with or without gene transfer, and determine the potential role of several miRNAs as biomarkers of acute rejection and immune tolerance...

BACKGROUND: Inappropriate matching of motor and sensory fibers after nerve repair or grafting can lead to nerve recovery failure. Identifying the motor and sensory fascicles enables surgeons to match them accurately and correctly align nerve stumps, which is crucial for neural regeneration. Very few methods have been reported to differentiate between the sensory and motor nerve fascicles, and the replicability of these techniques remains unestablished. In this study, we aimed to assess the accuracy of axonal cholinesterase (CE) histochemical staining in distinguishing motor and sensory nerve fibers...

Allogeneic hematopoietic cell transplantation (allo-HCT) offers a curative option for patients with certain non-malignant hematological diseases. High-dose post-transplant cyclophosphamide (PT-Cy) (200 mg/kg) and sirolimus (3 mg/kg), (HiC) synergistically induce stable mixed chimerism. Further, sirolimus and cytotoxic T lymphocyte-associated antigen-4 immunoglobulin (CTLA4-Ig), also known as Abatacept (Aba), promote immune tolerance and allograft survival. Here, in a major histocompatibility complex (MHC)-mismatched allo-HCT murine model, we combined Aba and/or T-cell depleting anti-Thy1...