INTRODUCTION: Despite the clinical success in vascularized composite allotransplantation (VCA), systemic immunosuppression remains necessary to prevent allograft rejection. Even with potent immunosuppressive regimens (tacrolimus, mycophenolate mofetil, and steroids), most patients experience several rejection episodes, often within the same year. The risk of systemic side effects must constantly be weighed against the risk of under-immunosuppression and, thus, acute and chronic rejection. In this context, genomic editing has emerged as a potential tool to minimize the need for toxic immunosuppressive regimens and has gained attention in the fields of solid organ transplantation and xenotransplantation. This strategy may also be relevant for the future of VCA. METHODS: We discuss the topic of genetic engineering and review recent developments in this field that justify investigating tools such as clustered regularly interspaced short palindromic repeats/Cas9 in the context of VCA. RESULTS: We propose specific strategies for VCA based on the most recent gene expression data. This includes the well-known strategy of tolerance induction. Specifically, targeting the interaction between antigen-presenting cells and recipient-derived T cells by CD40 knockout may be effective. The novelty for VCA is a discovery that donor-derived T lymphocytes may play a special role in allograft rejection of facial transplants. We suggest targeting these cells prior to transplantation (e.g., by ex vivo perfusion of the transplant) by knocking out genes necessary for the long-term persistence of donor-derived immune cells in the allograft. CONCLUSION: Despite the demonstrated feasibility of VCA in recent years, continued improvements to immunomodulatory strategies using tools like clustered regularly interspaced short palindromic repeats/Cas9 could lead to the development of approaches that mitigate the limitations associated with rejection of this life-giving procedure.
- MeSH
- genetické inženýrství MeSH
- homologní transplantace MeSH
- imunosupresiva terapeutické užití MeSH
- lidé MeSH
- rejekce štěpu prevence a kontrola MeSH
- transplantace orgánů * MeSH
- vaskularizovaná kompozitní alotransplantace * metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: The field of facial vascularized composite allotransplantation (fVCA) is still new and a limited number of patients have undergone the procedure. This has led to a lack of understanding about the impact of fVCA rejection on standard laboratory markers (e.g., CBC, BMP, CRP) for the acute management of these patients. It is not clear if rejection elicits a systemic inflammatory response that influences common inflammatory markers such as WBC and CRP. A comprehensive understanding of changes in these markers could help in the management of fVCA patients in the acute setting. METHODS: The medical records of 8 fVCA patients with a total of 9 transplants were reviewed retrospectively, and data on standard laboratory values (CBC, BMP, LFTs, CRP) and vital signs were extracted. To examine the relationship between laboratory values and rejection status, linear mixed models were used to analyze the data, taking into account their longitudinal nature (repeated measures). RESULTS: A statistically significant relationship was found between the Banff grade of rejection and the relative number of basophils in the patient's blood during rejection (p = 0.005). In addition, in patients with clinical signs of rejection (e.g., facial erythema, edema) and skin biopsy showing Banff ≥ II, CRP was found to be significantly elevated (p = 0.03). The WBC count remained stable during rejection, and the relative number of neutrophils was lower at the time of rejection, indicating possible consumption at the site of rejection. CONCLUSION: During fVCA rejection, most standard laboratory parameters and vital signs appear to be stable. However, the levels of CRP and basophils were elevated during rejection, while the neutrophil count was lower. Leukocytosis can likely be used as a marker of microbial infection in fVCA patients, as WBC does not seem to increase at the time of allograft rejection.
Allotransplantation of vascularized composite tissue is a new field of transplantation surgery. One application of this technique is abdominal wall transplantation used as a supplementary procedure to the transplantation of visceral organs in patients with abdominal compartment deficits. As abdominal wall closure problems are experienced in around 30-40% of such patients, peer reviewed conclusions on the viability of various options, are important for an informed choice of possible procedures. This review focuses on the abdominal wall allotransplantion procedure. Our search provided 35 appropriate references which we used to support our findings as follows: abdominal wall transplantation was performed in 33 patients at seven centres. Of these, 30 had a full thickness abdominal wall transplanted from the same donor, 3 from a second donor. Three had visceral organ transplants and in addition, the posterior sheet of the rectus muscle fascia. In summary, our findings were that abdominal wall allotransplantation does not jeopardize the outcome of visceral organs transplantation. There is no higher risk of complications or rejection of the visceral organs. There have been no fatalities as a direct result of complications due to abdominal wall transplantation. Finally, the transplanted abdominal wall may provide an early warning of rejection before diagnostic tests on the bowel are symptomatic.
- MeSH
- břišní stěna chirurgie MeSH
- imunosupresiva terapeutické užití MeSH
- lékařská praxe - způsoby provádění MeSH
- lidé MeSH
- mrtvola MeSH
- rejekce štěpu etiologie MeSH
- transplantace kůže metody MeSH
- vaskularizovaná kompozitní alotransplantace metody MeSH
- výběr dárců metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- dospělí MeSH
- experimenty na zvířatech MeSH
- larynx * transplantace MeSH
- lidé MeSH
- psi MeSH
- vaskularizovaná kompozitní alotransplantace metody MeSH
- výběr dárců MeSH
- zákroky plastické chirurgie metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- psi MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- dospělí MeSH
- lebka transplantace MeSH
- lidé MeSH
- skalp * transplantace MeSH
- skalpační poranění chirurgie MeSH
- transplantace izogenní metody MeSH
- vaskularizovaná kompozitní alotransplantace metody MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- dítě MeSH
- dospělí MeSH
- klouby ruky chirurgie MeSH
- klouby transplantace MeSH
- kolenní kloub chirurgie MeSH
- kryoprezervace MeSH
- lidé MeSH
- transplantace kostí metody MeSH
- uchovávání tkání MeSH
- vaskularizovaná kompozitní alotransplantace metody MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- imunosupresiva terapeutické užití MeSH
- lidé MeSH
- odběr tkání a orgánů MeSH
- periferní nervy * anatomie a histologie transplantace MeSH
- poranění periferního nervu chirurgie komplikace MeSH
- regenerace nervu imunologie účinky léků MeSH
- takrolimus terapeutické užití MeSH
- uchovávání tkání MeSH
- vaskularizovaná kompozitní alotransplantace metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- MeSH
- dospělí MeSH
- imunosupresiva terapeutické užití MeSH
- krk anatomie a histologie chirurgie MeSH
- laryngektomie MeSH
- lidé MeSH
- vaskularizovaná kompozitní alotransplantace * metody MeSH
- výsledek terapie MeSH
- zákroky plastické chirurgie metody MeSH
- zavedení chirurgických vývodů MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
