Mechanisms and Mediators of Inflammation: Potential Models for Skin Rejection and Targeted Therapy in Vascularized Composite Allotransplantation

Vascularized composite allotransplantation (VCA) is an effective treatment option for patients suffering from limb loss or severe disfigurement. However, postoperative courses of VCA recipients have been complicated by skin rejection, and long-term immunosuppression remains a necessity for allograft survival. To widen the scope of this quality-of-life improving procedure minimization of immunosuppression in order to limit risks and side effects is needed. In some aspects, the molecular mechanisms and dynamics of skin allograft rejection seem similar to inflammatory skin conditions. T cells are key players in skin rejection and are recruited to the skin via activation of adhesion molecules, cytokines, and chemokines. Blocking these molecules has not only shown success in the treatment of inflammatory dermatoses, but also prolonged graft survival in various models of solid organ transplantation. In addition to T cell recruitment, ectopic lymphoid structures within the allograft associated with chronic rejection in solid organ transplantation might contribute to the strong alloimmune response towards the skin. Selectively targeting the molecules involved offers exciting novel therapeutic options in the prevention and treatment of skin rejection after VCA.

Download Full-text

Positioning Vascularized Composite Allotransplantation within the Spectrum of Solid Organ Transplantation

10.21236/ada618393 ◽

2014 ◽

Author(s):

Christina L. Kaufman

Keyword(s):

Organ Transplantation ◽

Solid Organ Transplantation ◽

Solid Organ ◽

Vascularized Composite Allotransplantation

Download Full-text

Surgical Techniques for Revascularization in Abdominal Wall Transplantation

Journal of Reconstructive Microsurgery ◽

10.1055/s-0040-1709481 ◽

2020 ◽

Vol 36 (07) ◽

pp. 522-527

Author(s):

Andrew Atia ◽

Andrew Hollins ◽

Ronnie Shammas ◽

Brett T. Phillips ◽

Kadiyala V. Ravindra ◽

...

Keyword(s):

Abdominal Wall ◽

Organ Transplantation ◽

Abdominal Wall Reconstruction ◽

Solid Organ Transplantation ◽

Surgical Techniques ◽

Solid Organ ◽

Vascularized Composite Allotransplantation ◽

Ischemia Time ◽

Feasible Option ◽

Surgical Field

Abstract Background Abdominal wall vascularized composite allotransplantation (AW-VCA) can be considered as a technically feasible option for abdominal wall reconstruction in patients whose abdomen cannot be closed using traditional methods. However, successful initial abdominal wall revascularization in the setting of visceral organ transplantation can pose a major challenge as graft ischemia time, operating in a limited surgical field, and variable recipient and donor anatomy must be considered. Several techniques have been reported to accomplish abdominal wall revascularization. Methods A literature review was performed using PubMed for articles related to “abdominal wall transplantation (AWT).” The authors of this study sorted through this search for relevant publications that describe abdominal wall transplant anatomy, technical descriptions, and outcomes of various techniques. Results A total of four distinct revascularization techniques were found in the literature. Each of these techniques was described by the respective authors and reported varying patient outcomes. Levi et al published a landmark article in 2003 that described technical feasibility of AWT with anastomosis between donor external iliac and inferior epigastric vessels with recipient common iliac vessels in end-to-side fashion. Cipriani et al described a microsurgical technique with anastomosis between donor and recipient inferior epigastric vessels in an end-to-end fashion. Giele et al subsequently proposed banking the abdominal wall allograft in the forearm to reduce graft ischemia time. Recently, Erdmann et al described the utilization of an arteriovenous loop for synchronous revascularization of abdominal wall and visceral transplants for reduction of ischemia time, operative time, while eliminating the need for further operations. Conclusion Vascularized composite allotransplantation continues to advance with improving immunotherapy and outcomes in solid organ transplantation. Optimizing surgical techniques remains paramount as the field continues to grow. Refinement of the presented methods will continue as additional evidence and outcomes become available in AW-VCA.

Download Full-text

Tryptophan Metabolism via Kynurenine Pathway: Role in Solid Organ Transplantation

International Journal of Molecular Sciences ◽

10.3390/ijms22041921 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1921

Author(s):

Ruta Zulpaite ◽

Povilas Miknevicius ◽

Bettina Leber ◽

Kestutis Strupas ◽

Philipp Stiegler ◽

...

Keyword(s):

Organ Transplantation ◽

Immune Regulation ◽

Molecular Mechanisms ◽

Ischemia Reperfusion ◽

Solid Organ Transplantation ◽

Experimental Studies ◽

Disease Patient ◽

Kynurenine Pathway ◽

Current Evidence ◽

Solid Organ

Solid organ transplantation is a gold standard treatment for patients suffering from an end-stage organ disease. Patient and graft survival have vastly improved during the last couple of decades; however, the field of transplantation still encounters several unique challenges, such as a shortage of transplantable organs and increasing pool of extended criteria donor (ECD) organs, which are extremely prone to ischemia-reperfusion injury (IRI), risk of graft rejection and challenges in immune regulation. Moreover, accurate and specific biomarkers, which can timely predict allograft dysfunction and/or rejection, are lacking. The essential amino acid tryptophan and, especially, its metabolites via the kynurenine pathway has been widely studied as a contributor and a therapeutic target in various diseases, such as neuropsychiatric, autoimmune disorders, allergies, infections and malignancies. The tryptophan-kynurenine pathway has also gained interest in solid organ transplantation and a variety of experimental studies investigating its role both in IRI and immune regulation after allograft implantation was first published. In this review, the current evidence regarding the role of tryptophan and its metabolites in solid organ transplantation is presented, giving insights into molecular mechanisms and into therapeutic and diagnostic/prognostic possibilities.

Download Full-text