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1.
J Vis Exp ; (197)2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37677007

RESUMO

Endocardial fibroelastosis (EFE), defined by subendocardial tissue accumulation, has major impacts on the development of the left ventricle (LV) and precludes patients with congenital critical aortic stenosis and hypoplastic left heart syndrome (HLHS) from curative anatomical biventricular surgical repair. Surgical resection is currently the only available therapeutic option, but EFE often recurs, sometimes with an even more infiltrative growth pattern into the adjacent myocardium. To better understand the underlying mechanisms of EFE and to explore therapeutic strategies, an animal model suitable for preclinical testing was developed. The animal model takes into consideration that EFE is a disease of the immature heart and is associated with flow disturbances, as supported by clinical observations. Thus, the heterotopic heart transplantation of neonatal rat donor hearts is the basis for this model. A neonatal rat heart is transplanted into an adolescent rat's abdomen and connected to the recipient's infrarenal aorta and inferior vena cava. While perfusion of the coronary arteries preserves the viability of the donor heart, flow stagnation within the LV induces EFE growth in the very immature heart. The underlying mechanism of EFE formation is the transition of endocardial endothelial cells to mesenchymal cells (EndMT), which is a well-described mechanism of early embryonic development of the valves and septa but also the leading cause of fibrosis in heart failure. EFE formation can be macroscopically observed within days after transplantation. Transabdominal echocardiography is used to monitor the graft viability, contractility, and the patency of the anastomoses. Following euthanasia, the EFE tissue is harvested, and it shows the same histopathological characteristics as human EFE tissue from HLHS patients. This in vivo model allows for studying the mechanisms of EFE development in the heart and testing treatment options to prevent this pathological tissue formation and provides the opportunity for a more generalized examination of EndMT-induced fibrosis.


Assuntos
Estenose da Valva Aórtica , Transplante de Coração , Adolescente , Feminino , Gravidez , Humanos , Animais , Ratos , Células Endoteliais , Doadores de Tecidos , Transplante Heterotópico , Coração
2.
J Vis Exp ; (196)2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37335093

RESUMO

Over the past 50 years, many researchers have reported heterotopic abdominal heart transplantation in mice and rats, with some variations in the surgical technique. Modifying the transplantation procedure to strengthen the myocardial protection could prolong the ischemia time while preserving the donor's cardiac function. This technique's key points are as follows: transecting the donor's abdominal aorta before harvesting to unload the donor's heart; perfusing the donor's coronary arteries with a cold cardioplegic solution; and topical cooling of the donor's heart during the anastomosis procedure. Consequently, since this procedure prolongs the acceptable ischemia time, beginners can easily perform it and achieve a high success rate. Moreover, a new aortic regurgitation (AR) model was established in this work using a technique different from the existing one, which is created by inserting a catheter from the right carotid artery and puncturing the native aortic valve under continuous echocardiographic guidance. A heterotopic abdominal heart transplantation was performed using the novel AR model. In the protocol, after the donor's heart is harvested, a stiff guidewire is inserted into the donor's brachiocephalic artery and advanced toward the aortic root. The aortic valve is punctured by pushing the guidewire further even after the resistance is felt, thus inducing AR. It is easier to damage the aortic valve using this method than with the procedure described in the conventional AR model. Additionally, this novel AR model does not contribute to the recipient's circulation; therefore, this method is expected to produce a more severe AR model than the conventional procedure.


Assuntos
Insuficiência da Valva Aórtica , Cardiopatias Congênitas , Transplante de Coração , Ratos , Animais , Camundongos , Transplante de Coração/métodos , Insuficiência da Valva Aórtica/cirurgia , Miocárdio , Aorta Abdominal , Transplante Heterotópico/métodos , Isquemia
4.
J Vis Exp ; (191)2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36715410

RESUMO

Laryngeal heterotopic transplantation, although a technically challenging procedure, offers more scientific analysis and cost benefits compared to other animal models. Although first described by Shipchandler et al. in 2009, this technique is not widely used, possibly due to the difficulties in learning the microsurgical technique and time required to master it. This paper describes the surgical steps in detail, as well as potential pitfalls to avoid, in order to encourage effective use of this technique. In this model, the bilateral carotid arteries of the donor larynx are anastomosed to the recipient carotid artery and external jugular vein, allowing for blood flow through the graft. Blood flow can be confirmed intraoperatively by the visualization of blood filling in the graft bilateral carotid arteries, reddening of the thyroid glands of the graft, and bleeding from micro vessels in the graft. The crucial elements for success include delicate preservation of the graft vessels, making the correct size arteriotomy and venotomy, and using the appropriate number of sutures on the arterial-arterial and arterial-venous anastomoses to secure vessels without leakage and prevent occlusion. Anyone can become proficient in this model with sufficient training and perform the procedure in approximately 3 h. If performed successfully, this model allows for immunologic studies to be performed with ease and at low cost.


Assuntos
Transplante de Coração , Laringe , Camundongos , Animais , Modelos Animais de Doenças , Transplante de Coração/métodos , Transplante Heterotópico/métodos , Procedimentos Cirúrgicos Vasculares/métodos , Laringe/cirurgia , Anastomose Cirúrgica/métodos
5.
J Vis Exp ; (187)2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36282719

RESUMO

The development of experimental models of cardiac transplantation in animals has contributed to many advances in the fields of immunology and solid organ transplantation. While the heterotopic vascularized murine cardiac transplantation model was initially utilized in studies of graft rejection using combinations of mismatched inbred mouse strains, access to genetically modified strains and therapeutic modalities can provide powerful new preclinical insights. Fundamentally, the surgical methodology for this technique has not changed since its development, especially with respect to important factors such as aseptic technique, anesthesia, and analgesia, which make material impacts on postsurgical morbidity and mortality. Additionally, improvements in perioperative management are expected to provide improvements in both animal welfare and experimental outcomes. This paper reports upon a protocol developed in collaboration with a subject matter expert in veterinary anesthesia and describes the surgical technique with an emphasis on perioperative management. Additionally, we discuss the implications of these refinements and provide details on troubleshooting critical surgical steps for this procedure.


Assuntos
Analgesia , Anestesia , Transplante de Coração , Camundongos , Animais , Transplante de Coração/métodos , Transplante Heterotópico/métodos , Rejeição de Enxerto , Camundongos Endogâmicos , Controle de Infecções
6.
J Vis Exp ; (184)2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35815977

RESUMO

Murine models of cardiac transplantation are frequently utilized to study ischemia-reperfusion injury, innate and adaptive immune responses after transplantation, and the impact of immunomodulatory therapies on graft rejection. Heterotopic cervical heart transplantation in mice was first described in 1991 using sutured anastomoses and subsequently modified to include cuff techniques. This modification allowed for improved success rates, and since then, there have been multiple reports that have proposed further technical improvements. However, translation into more widespread utilization remains limited due to the technical difficulty associated with graft anastomoses, which requires precision to achieve adequate length and caliber of the cuffs to avoid vascular anastomotic twisting or excessive tension, which can result in damage to the graft. The present protocol describes a modified technique for performing heterotopic cervical cardiac transplantation in mice which involves cuff placement on the recipient's common carotid artery and the donor's pulmonary artery in alignment with the direction of the blood flow.


Assuntos
Transplante de Coração , Transplante Heterotópico , Animais , Artéria Carótida Primitiva/cirurgia , Rejeição de Enxerto , Transplante de Coração/métodos , Camundongos , Pescoço/cirurgia , Transplante Heterotópico/métodos
7.
J Vis Exp ; (183)2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35661103

RESUMO

The objective of this protocol is to set up a rat heterotopic heart transplantation model with donation after circulatory death (DCD) donor hearts. There are two setups for this protocol: heart donor setup and recipient setup. In the heart donor setup, Sprague Dawley rats are anesthetized, endotracheally intubated, and ventilated. The right carotid artery is cannulated to deliver heparin and the paralytic agent vecuronium-bromide. The DCD process is initiated by terminating the ventilation. After 20 min, the heart is exposed and the aorta distal to the brachiocephalic branch is clamped. At 25 min from terminating the ventilator, ice-cold University of Wisconsin (UW) solution is perfused through the carotid catheter to flush the heart. The heart is procured by dividing the aorta, pulmonary artery, venae cavae, and pulmonary veins and stored in UW solution for implantation. In the recipient setup, the Lewis rat is anesthetized with isoflurane. Slow-release buprenorphine is administered subcutaneously to facilitate a smooth postoperative recovery. Through a midline abdominal incision, the infra-renal aorta and the inferior vena cava are isolated and clamped with an atraumatic vascular clamp. The donor heart aorta and pulmonary artery are sutured to the recipient abdominal aorta and vena cava, respectively, with a running 8-0 Prolene. The vascular clamp is removed to reperfuse the heart. The abdominal wall is closed and the rat is recovered. After a set interval (24 h to 2 weeks), the recipient rat is anesthetized, the transplanted heart is exposed, and a balloon-tip-catheter is inserted into the left ventricle via the apex to record developed pressure and dP/dt using a data acquisition system. The heart tissue is collected for histology, immunology, or molecular analysis. A successful DCD donor rat heart transplantation model will allow further studies on the cardioprotective approaches to improve heart transplantation outcomes from DCD donors.


Assuntos
Transplante de Coração , Adenosina , Alopurinol , Animais , Glutationa , Coração , Transplante de Coração/métodos , Humanos , Insulina , Soluções para Preservação de Órgãos , Rafinose , Ratos , Ratos Endogâmicos Lew , Ratos Sprague-Dawley , Doadores de Tecidos , Transplante Heterotópico/métodos
9.
J Vis Exp ; (180)2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35225284

RESUMO

Cardiac transplantation is the gold standard treatment for end-stage heart failure. However, it remains limited by the number of available donor hearts and complications such as primary graft dysfunction and graft rejection. The recent clinical use of an ex vivo perfusion device in cardiac transplantation introduces a unique opportunity for treating cardiac allografts with therapeutic interventions to improve function and avoid deleterious recipient responses. Establishing a translational, large-animal model for therapeutic delivery to the entire allograft is essential for testing novel therapeutic approaches in cardiac transplantation. The porcine, heterotopic heart transplantation model in the intraabdominal position serves as an excellent model for assessing the effects of novel interventions and the immunopathology of graft rejection. This model additionally offers long-term survival for the pig, given that the graft is not required to maintain the recipient's circulation. The aim of this protocol is to provide a reproducible and robust approach for achieving ex vivo delivery of a therapeutic to the entire cardiac allograft prior to transplantation and provide technical details to perform a survival heterotopic transplant of the ex vivo perfused heart.


Assuntos
Transplante de Coração , Aloenxertos , Animais , Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Coração/métodos , Humanos , Suínos , Doadores de Tecidos , Transplante Heterotópico
10.
J Vis Exp ; (180)2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35188131

RESUMO

Cardiac allograft rejection limits the long-term survival of patients after heart transplantation. A mouse heart transplantation model is ideal for investigating the mechanism of cardiac allograft rejection in preclinical studies because of their high homology with human genes. This understanding would help develop unique approaches to improving patients' long-term survival treated with cardiac allografts. In a mouse model, abdominal donor heart implantation is commonly performed with an end-to-side anastomosis to the recipient's aorta and inferior vena cava using stitches. In this model, the donor's heart is implanted by end-to-end anastomosis to the recipient's carotid artery and jugular vein by the modified-Cuff technique. The transplantation surgery is performed without stitching and thus may increase the survival of the recipient since there is no interference with the blood supply and venous reflux of the lower body. This mouse model would help investigate the mechanisms underlying the immunological and pathological (acute/chronic) rejection of cardiac allografts.


Assuntos
Transplante de Coração , Anastomose Cirúrgica/métodos , Animais , Modelos Animais de Doenças , Transplante de Coração/métodos , Humanos , Camundongos , Doadores de Tecidos , Transplante Heterotópico/métodos
11.
Reprod Biol Endocrinol ; 20(1): 35, 2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35183206

RESUMO

BACKGROUND: Ovarian tissue cryopreservation and transplantation (OTCTP) is currently the main option available to preserve fertility in prepubertal patients undergoing aggressive cancer therapy treatments. However, a major limitation of OTCTP is follicle loss after transplantation. The mouse is a model of choice for studying ovarian function and follicle development after ovarian tissue grafting in vivo. In these mouse models, ovarian tissue or ovaries can be transplanted to different sites. Our aim was to evaluate a new alternative to heterotopic transplantation models that could be useful to test pharmaceutical improvement for ovarian grafts after OTCTP. METHODS: Slow frozen murine whole ovaries were transplanted into the mouse ears (between the external ear skin layer and the cartilage). Ovarian transplants were recovered after 3, 14 or 21 days. Grafts were analyzed by immunohistochemistry and follicle density analyses were performed. RESULTS: An increase of ovarian vascularization (CD31 and Dextran-FITC positive staining), as well as cellular proliferation (Ki67 staining) were observed 3 weeks after transplantation in comparison to 3 days. Fibrosis density, evaluated after Van Gieson staining, decreased 3 weeks after transplantation. Furthermore, transplantation of cryopreserved ovaries into ovariectomized mice favored follicle activation compared to transplantation into non-ovariectomized mice. CONCLUSION: The present study indicates that surgical tissue insertion in the highly vascularized murine ear is an effective model for ovarian grafting. This model could be helpful in research to test pharmaceutical strategies to improve the function and survival of cryopreserved and transplanted ovarian tissue.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Fármacos para a Fertilidade Feminina/uso terapêutico , Preservação da Fertilidade/métodos , Ovário/transplante , Transplante Heterotópico/métodos , Animais , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Terapia de Reposição Hormonal/métodos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Modelos Biológicos
12.
J Am Soc Nephrol ; 33(1): 186-200, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725107

RESUMO

BACKGROUND: Tertiary lymphoid tissues (TLTs) are ectopic lymphoid tissues found in chronically inflamed organs. Although studies have documented TLT formation in transplanted kidneys, the clinical relevance of these TLTs remains controversial. We examined the effects of TLTs on future graft function using our histologic TLT maturity stages and the association between TLTs and Banff pathologic scores. We also analyzed the risk factors for the development of TLTs. METHODS: Serial protocol biopsy samples (0 hour, 1, 6, and 12 months) without rejection were retrospectively analyzed from 214 patients who underwent living donor kidney transplantation. TLTs were defined as lymphocyte aggregates with signs of proliferation and their stages were determined by the absence (stage I) or presence (stage II) of follicular dendritic cells. RESULTS: Only 4% of patients exhibited TLTs at the 0-hour biopsy. Prevalence increased to almost 50% at the 1-month biopsy, and then slightly further for 12 months. The proportion of advanced stage II TLTs increased gradually, reaching 19% at the 12-month biopsy. Presence of stage II TLTs was associated with higher risk of renal function decline after transplantation compared with patients with no TLT or stage I TLTs. Stage II TLTs were associated with more severe tubulitis and interstitial fibrosis/tubular atrophy at 12 months and predicted poorer graft function independently from the degree of interstitial inflammation. Pretransplantation rituximab treatment dramatically attenuated the development of stage II TLTs. CONCLUSIONS: TLTs are commonly found in clinically stable transplanted kidneys. Advanced stage II TLTs are associated with progressive graft dysfunction, independent of interstitial inflammation.


Assuntos
Coristoma/patologia , Nefropatias/patologia , Transplante de Rim/efeitos adversos , Tecido Linfoide , Disfunção Primária do Enxerto/etiologia , Disfunção Primária do Enxerto/patologia , Adulto , Idoso , Biópsia , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
J Vis Exp ; (175)2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34633389

RESUMO

There is an urgent clinical need for heart valve replacements that can grow in children. Heart valve transplantation is proposed as a new type of transplant with the potential to deliver durable heart valves capable of somatic growth with no requirement for anticoagulation. However, the immunobiology of heart valve transplants remains unexplored, highlighting the need for animal models to study this new type of transplant. Previous rat models for heterotopic aortic valve transplantation into the abdominal aorta have been described, though they are technically challenging and costly. For addressing this challenge, a renal subcapsular transplant model was developed in rodents as a practical and more straightforward method for studying heart valve transplant immunobiology. In this model, a single aortic valve leaflet is harvested and inserted into the renal subcapsular space. The kidney is easily accessible, and the transplanted tissue is securely contained in a subcapsular space that is well vascularized and can accommodate a variety of tissue sizes. Furthermore, because a single rat can provide three donor aortic leaflets and a single kidney can provide multiple sites for transplanted tissue, fewer rats are required for a given study. Here, the transplantation technique is described, providing a significant step forward in studying the transplant immunology of heart valve transplantation.


Assuntos
Transplante de Coração , Roedores , Animais , Valva Aórtica/cirurgia , Modelos Animais , Ratos , Transplante Heterotópico
15.
Front Immunol ; 12: 710904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421916

RESUMO

Although studies in oncology have well explored the pharmacological effects of Birc5, little is known about its role in allogeneic T-cell responses. Therefore, the present study used a mouse model of acute heart allograft rejection to investigate the protective effect and mechanism of conditional knockout of Birc5 in T cells. Survivin (encoded by Birc5) was up-regulated in T cells activated in vivo and in vitro. Deletion of Birc5 in T cells attenuated acute heart allograft rejection by reducing the ratio of effector to naive T cells and Th1 to Tregs. In addition, deletion of Birc5 had no noticeable effect on proliferation but on apoptosis and the secretion of IFN-γ. The results revealed a significant increase in the percentage of Annexin V positive CD4+ T cells in the Birc5-/- group, compared to the WT. Moreover, there was significant increase in early apoptotic alloreactive T cells in Birc5-/- mice and this was partly mediated by caspase-3. Furthermore, treatment with YM155 inhibited acute heart allograft rejection in vivo and increased T-cell apoptosis in healthy human PBMCs in vitro. The results highlight a potential therapeutic target for the prevention and treatment of acute transplant rejection.


Assuntos
Apoptose , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/efeitos adversos , Survivina/fisiologia , Linfócitos T/imunologia , Doença Aguda , Animais , Caspase 3/fisiologia , Imidazóis/farmacologia , Interferon gama/biossíntese , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Naftoquinonas/farmacologia , Transplante Heterotópico
16.
J Vis Exp ; (172)2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34152314

RESUMO

The surgical technique of heterotopic abdominal heart transplantation in mice is a standard model for research in transplantation immunology. Here, the established technique for a modified blood circuit reconstruction in a heterotopic abdominal heart transplantation model is presented. This method uses the intrathoracic inferior vena cava (IIVC) instead of the pulmonary artery of the donor heart for the anastomosis to the inferior vena cava of the recipient. It is facilitating and improving success rates for abdominal heart transplantation in mice.


Assuntos
Transplante de Coração , Abdome/cirurgia , Anastomose Cirúrgica , Animais , Humanos , Camundongos , Doadores de Tecidos , Transplante Heterotópico , Veia Cava Inferior/cirurgia
17.
J Vis Exp ; (172)2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34180905

RESUMO

Vascularized composite allotransplantations (VCA) represent the most advanced reconstruction option for patients without autologous surgical possibilities after a complex tissue defect. Face and hand transplantations have changed disfigured patients' lives, giving them a new aesthetic and functional social organ. Despite promising outcomes, VCA is still underperformed due to life-long immunosuppression comorbidities and infectious complications. The rat is an ideal animal model for in vivo studies investigating immunological pathways and graft rejection mechanisms. Rats are also widely used in novel composite tissue graft preservation techniques, including perfusion and cryopreservation studies. Models used for VCA in rats must be reproducible, reliable, and efficient with low postoperative morbidity and mortality. Heterotopic limb transplantation procedures fulfill these criteria and are easier to perform than orthotopic limb transplants. Mastering rodent microsurgical models requires solid experience in microsurgery and animal care. Herein is reported a reliable and reproducible model of partial heterotopic osteomyocutaneous flap transplantation in rats, the postoperative outcomes, and the means of prevention of potential complications.


Assuntos
Alotransplante de Tecidos Compostos Vascularizados , Animais , Rejeição de Enxerto , Membro Posterior , Humanos , Terapia de Imunossupressão , Ratos , Transplante Heterotópico
18.
J Cardiovasc Pharmacol ; 77(5): 614-620, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33951698

RESUMO

ABSTRACT: Acute immune rejection is one of the most serious complications of heart transplantation, and its mechanism has always been a hot spot. Th17 cells and cytokine interleukin-17 (IL-17) have been proved to be involved in acute immune rejection, and the signaling pathway mechanism has attracted our interest. It has been confirmed that the Janus kinase 2-signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway is involved in the differentiation of CD4+ T cells, so we focus on whether the JAK2/STAT3 signaling pathway is involved in the occurrence of acute immune rejection by regulating the Th17/IL-17 axis. In this study, we used Bagg's Albino c mice and C57BL/6 mice to construct heterotopic heart transplantation models, which were divided into the acute rejection group and AG490-treated group (n = 5), and donor tissue and serum were collected in 3 experimental days from the recipient mice for H&E staining analysis of paraffin sections and ELISA, Western blot, flow cytometry, and real time-polymerase chain reaction. The results showed that the acute rejection rating of the heart decreased, and the expression of related factors decreased significantly after using the inhibitor AG490, suggesting that the JAK2/STAT3 signaling pathway regulates expression of the Th17/IL-17 axis in cardiac allograft rejection.


Assuntos
Rejeição de Enxerto/prevenção & controle , Transplante de Coração , Imunossupressores/farmacologia , Interleucina-17/metabolismo , Janus Quinase 2/antagonistas & inibidores , Inibidores de Janus Quinases/farmacologia , Miocárdio/enzimologia , Fator de Transcrição STAT3/metabolismo , Células Th17/metabolismo , Tirfostinas/farmacologia , Animais , Modelos Animais de Doenças , Rejeição de Enxerto/enzimologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/efeitos dos fármacos , Janus Quinase 2/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Miocárdio/imunologia , Miocárdio/patologia , Transdução de Sinais , Células Th17/imunologia , Transplante Heterotópico
19.
Arch Esp Urol ; 74(3): 293-298, 2021 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-33818425

RESUMO

OBJECTIVE: Kidney transplant is the treatmentof election of end-stage chronic renal disease, usually being heterotopic extraperitoneal in the iliac fossae, with successful results. This technique can be challenging or even not feasible, usually in cases of severe vasculopathy or previous grafts, so urologists should consider alternatives such as orthotopic transplant. MATERIAL AND METHODS: We present three cases oforthotopic kidney transplant (OKT) made in Cruces University Hospital from 2001 to 2019, out of 2580 cases. We review recipients' medical history, indication,surgical technique and post surgical evolution. RESULTS: The average age of the patients was 51.6 years. The indication was severe vasculopathy of iliac vessels. We made left nephrectomy, followed by venous renal end-to-end anastomosis, arterial end-to-side anastomosis to aorta and pyelo-pyelic anastomosis with catheter,with immediate function of the graft. The patients' evolution was favourable, without significant complications and no differences with heterotopic transplant. CONCLUSION: OKT is a good alternative when heterotopicis not feasible, with an acceptable number of complications and similar survival.


OBJETIVO: El trasplante renal es el tratamiento de elección de la enfermedad renal crónica terminal. Habitualmente es heterotópico extraperitoneal en fosa ilíaca, presentando buenos resultados. En ocasiones no es factible (por vasculopatía severa, espacio reducido por injertos previos…), habiendo que considerar otras técnicas, como el trasplante ortotópico. MATERIAL Y MÉTODOS: Revisión retrospectiva de los trasplantes renales ortotópicos (TRO) realizados en el Hospital Universitario Cruces entre 2001 y 2019, de un total de 2580 trasplantes. Se revisa la historia clínica, indicación, técnica quirúrgica, evolución y complicaciones. RESULTADOS: Tres pacientes con media de 51,6 años se sometieron a trasplante ortotópico por vasculopatía severa de vasos ilíacos. Se realizó nefrectomía izquierda y anastomosis venosa termino-terminal a vena renal propia, arterial termino-lateral a aorta y pielo-piélica con catéter, presentando función inmediata. La evolución fue favorable, sin complicaciones significativas y sin diferencias con el trasplante heterotópico. CONCLUSIÓN: El TRO es una buena alternativa cuando el heterotópico no es factible, con un número aceptable de complicaciones y supervivencia similar.


Assuntos
Falência Renal Crônica , Transplante de Rim , Anastomose Cirúrgica , Aorta , Humanos , Rim , Falência Renal Crônica/cirurgia , Pessoa de Meia-Idade
20.
Cell Rep ; 35(2): 108967, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33852867

RESUMO

T lymphocyte differentiation in the steady state is characterized by high cellular turnover whereby thymocytes do not self-renew. However, if deprived of competent progenitors, the thymus can temporarily maintain thymopoiesis autonomously. This bears a heavy cost, because prolongation of thymus autonomy causes leukemia. Here, we show that, at an early stage, thymus autonomy relies on double-negative 3 early (DN3e) thymocytes that acquire stem-cell-like properties. Following competent progenitor deprivation, DN3e thymocytes become long lived, are required for thymus autonomy, differentiate in vivo, and include DNA-label-retaining cells. At the single-cell level, the transcriptional programs of thymopoiesis in autonomy and the steady state are similar. However, a new cell population emerges in autonomy that expresses an aberrant Notch target gene signature and bypasses the ß-selection checkpoint. In summary, DN3e thymocytes have the potential to self-renew and differentiate in vivo if cell competition is impaired, but this generates atypical cells, probably the precursors of leukemia.


Assuntos
Hematopoese/genética , Leucemia/genética , Receptores Notch/genética , Timócitos/imunologia , Timo/imunologia , Fatores de Transcrição/genética , Animais , Diferenciação Celular , Proliferação de Células , Família de Proteínas EGF/genética , Família de Proteínas EGF/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hematopoese/imunologia , Humanos , Imunofenotipagem , Rim , Leucemia/imunologia , Leucemia/patologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores Notch/imunologia , Transdução de Sinais , Análise de Célula Única , Timócitos/classificação , Timócitos/patologia , Timo/patologia , Timo/transplante , Fatores de Transcrição/imunologia , Transplante Heterotópico , Transplante Homólogo
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