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1.
Am J Transplant ; 21(10): 3211-3212, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34624183

Assuntos
Transplantes
2.
Sci Rep ; 11(1): 17989, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504254

RESUMO

Prevascularized artificial three-dimensional (3D) tissues are effective biomaterials for regenerative medicine. We have previously established a scaffold-free 3D artificial vascular tissue from normal human dermal fibroblasts (NHDFs) and umbilical vein-derived endothelial cells (HUVECs) by layer-by-layer cell coating technique. In this study, we constructed an artificial vascular tissue constructed by human adipose tissue-derived stromal cells (hASCs) and HUVECs (ASCVT) by a modified technique with cryopreservation. ASCVT showed a higher thickness with more dense vascular networks than the 3D tissue based on NHDFs. Correspondingly, 3D-cultured ASCs showed higher expression of several angiogenesis-related factors, including vascular endothelial growth factor-A and hepatic growth factor, compared to that of NHDFs. Moreover, perivascular cells in ASCVT were detected by pericyte markers, suggesting the differentiation of hASCs into pericyte-like cells. Subcutaneous transplantation of ASCVTs to nude mice resulted in an engraftment with anastomosis of host's vascular structures at 2 weeks after operation. In the engrafted tissue, the vascular network was surrounded by mural-like structure-forming hASCs, in which some parts developed to form vein-like structures at 4 weeks, suggesting the generation of functional vessel networks. These results demonstrated that cryopreserved human cells, including hASCs, could be used directly to construct the artificial transplantable tissue for regenerative medicine.


Assuntos
Criopreservação/métodos , Células Endoteliais da Veia Umbilical Humana , Células-Tronco Mesenquimais , Engenharia Tecidual/métodos , Transplantes/citologia , Animais , Células Cultivadas , Feminino , Fibroblastos , Proteínas de Fluorescência Verde/genética , Humanos , Recém-Nascido , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Animais , Medicina Regenerativa/métodos , Tecidos Suporte , Transplante de Tecidos/métodos , Transfecção , Resultado do Tratamento
3.
Cell Transplant ; 30: 9636897211045320, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34565192

RESUMO

In this Commentary, we echo the conclusions of a recent review titled "The promise of stem cell-derived islet replacement therapy," which highlighted recent advances in producing glucose responsive "islets" from stem cells and the benefits of their use in islet transplant therapy in type 1 diabetes (T1D). The review also outlined the status of clinical islet transplantation and the challenges that have prevented it from reaching its full therapeutic promise. We agree with the conclusions of the review and suggest that the identified challenges may be overcome by using the eye anterior chamber as an islet transplant site. We anticipate that the combination of stem cell-derived islets and intraocular transplant could help this promising T1D therapy reach full fruition.


Assuntos
Diabetes Mellitus Tipo 1 , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Transplantes , Diabetes Mellitus Tipo 1/terapia , Humanos , Células-Tronco
4.
Transpl Infect Dis ; 23(5): e13738, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34590768
5.
Sci Rep ; 11(1): 17930, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504136

RESUMO

Kidney transplantation with grafts procured after donation-after-cardiac death (DCD) has led to an increase in incidence of delayed graft function (DGF). It is thought that the warm ischemic (WI) insult encountered during DCD procurement is the cause of this finding, although few studies have been designed to definitely demonstrate this causation in a transplantation setting. Here, we use a large animal renal transplantation model to study the effects of prolonged WI during procurement on post-transplantation renal function. Kidneys from 30 kg-Yorkshire pigs were procured following increasing WI times of 0 min (Heart-Beating Donor), 30 min, 60 min, 90 min, and 120 min (n = 3-6 per group) to mimic DCD. Following 8 h of static cold storage and autotransplantation, animals were followed for 7-days. Significant renal dysfunction (SRD), resembling clinical DGF, was defined as the development of oliguria < 500 mL in 24 h from POD3-4 along with POD4 serum potassium > 6.0 mmol/L. Increasing WI times resulted in incremental elevation of post-operative serum creatinine that peaked later. DCD120min grafts had the highest and latest elevation of serum creatinine compared to all groups (POD5: 19.0 ± 1.1 mg/dL, p < 0.05). All surviving animals in this group had POD4 24 h urine output < 500 cc (mean 235 ± 172 mL) and elevated serum potassium (7.2 ± 1.1 mmol/L). Only animals in the DCD120min group fulfilled our criteria of SRD (p = 0.003), and their renal function improved by POD7 with 24 h urine output > 500 mL and POD7 serum potassium < 6.0 mmol/L distinguishing this state from primary non-function. In a transplantation survival model, this work demonstrates that prolonging WI time similar to that which occurs in DCD conditions contributes to the development of SRD that resembles clinical DGF.


Assuntos
Morte , Função Retardada do Enxerto/etiologia , Transplante de Rim/métodos , Índice de Gravidade de Doença , Doadores de Tecidos , Transplantes/irrigação sanguínea , Isquemia Quente/efeitos adversos , Animais , Creatinina/sangue , Função Retardada do Enxerto/sangue , Sobrevivência de Enxerto , Falência Renal Crônica/cirurgia , Modelos Animais , Preservação de Órgãos/métodos , Perfusão/métodos , Potássio/sangue , Suínos , Fatores de Tempo , Transplante Autólogo/métodos , Resultado do Tratamento
6.
Transpl Infect Dis ; 23(5): e13721, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34463013

RESUMO

Organ procurement organizations (OPOs) evaluate referrals for deceased organ donation in the United States. Efforts to expand the donor pool, such as the HIV organ policy equity (HOPE) Act that permits transplants from HIV-positive donors to HIV-positive recipients, can only succeed if OPOs pursue referrals. However, relatively little is known about how OPO staff evaluate referrals. To better understand this process, OPO staff completed a discrete choice experiment to quantify the relative importance of seven donor characteristics on the decision to pursue a theoretical donor. Relative importance was defined by Partworth utility using a hierarchical Bayesian conditional logit model. There were 51 respondents from 36 of 58 OPOs in the United States. Of the seven attributes, organ and tissue potential were the most influential, followed by age, type of death, HIV status, donor registration, and Hepatitis C status. To be preferred to an HIV-negative donor, an HIV-positive donor needed to have the potential to donate two additional organs. These data provide insight into the preferences of OPO referral staff and may help explain the lower than expected number of HIV-positive transplants performed since the passage of the HOPE Act.


Assuntos
Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Transplantes , Teorema de Bayes , Humanos , Doadores de Tecidos , Estados Unidos
7.
Curr Opin Organ Transplant ; 26(5): 547-553, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34411039

RESUMO

PURPOSE OF REVIEW: The Final Rule clearly states that geography should not be a determinant of a chance of a potential candidate being transplanted. There have been multiple concerns about geographic disparities in patients in need of solid organ transplantation. Allocation policy adjustments have been designed to address these concerns, but there is little evidence that the disparities have been solved. The purpose of this review is to describe the main drivers of geographic disparities in solid organ transplantation and how allocation policy changes and other potential actions could impact these inequalities. RECENT FINDINGS: Geographical disparities have been reported in kidney, pancreas, liver, and lung transplantation. Organ Procurement and Transplant Network has modified organ allocation rules to underplay geography as a key determinant of a candidates' chance of receiving an organ. Thus, heart, lung, and more recently liver and Kidney Allocation Systems have incorporated broader organ sharing to reduce geographical disparities. Whether these policy adjustments will indeed eliminate geographical disparities are still unclear. SUMMARY: Modern allocation policy focus in patients need, regardless of geography. Innovative actions to further reduce geographical disparities are needed.


Assuntos
Transplante de Pulmão , Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Transplantes , Humanos , Doadores de Tecidos , Estados Unidos , Listas de Espera
8.
Biomolecules ; 11(7)2021 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-34356674

RESUMO

The discovery and application of antibiotics in the common clinical practice has undeniably been one of the major medical advances in our times. Their use meant a drastic drop in infectious diseases-related mortality and contributed to prolonging human life expectancy worldwide. Nevertheless, antibiotics are considered by many a double-edged sword. Their extensive use in the past few years has given rise to a global problem: antibiotic resistance. This factor and the increasing evidence that a wide range of antibiotics can damage mammalian mitochondria, have driven a significant sector of the medical and scientific communities to advise against the use of antibiotics for purposes other to treating severe infections. Notwithstanding, a notorious number of recent studies support the use of these drugs to treat very diverse conditions, ranging from cancer to neurodegenerative or mitochondrial diseases. In this context, there is great controversy on whether the risks associated to antibiotics outweigh their promising beneficial features. The aim of this review is to provide insight in the topic, purpose for which the most relevant findings regarding antibiotic therapies have been discussed.


Assuntos
Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Envelhecimento , Antibacterianos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Transtornos Mentais/induzido quimicamente , Transtornos Mentais/microbiologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Doenças Mitocondriais/tratamento farmacológico , Doenças Mitocondriais/patologia , Fadiga Muscular/efeitos dos fármacos , Neoplasias/induzido quimicamente , Neoplasias/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Obesidade/induzido quimicamente , Transplantes
9.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445075

RESUMO

Pre-weaned porcine islets (PPIs) represent an unlimited source for islet transplantation but are functionally immature. We previously showed that necrostatin-1 (Nec-1) immediately after islet isolation enhanced the in vitro development of PPIs. Here, we examined the impact of Nec-1 on the in vivo function of PPIs after transplantation in diabetic mice. PPIs were isolated from pancreata of 8-15-day-old, pre-weaned pigs and cultured in media alone, or supplemented with Nec-1 (100 µM) on day 0 or on day 3 of culture (n = 5 for each group). On day 7, islet recovery, viability, oxygen consumption rate, insulin content, cellular composition, insulin secretion capacity, and transplant outcomes were evaluated. While islet viability and oxygen consumption rate remained high throughout 7-day tissue culture, Nec-1 supplementation on day 3 significantly improved islet recovery, insulin content, endocrine composition, GLUT2 expression, differentiation potential, proliferation capacity of endocrine cells, and insulin secretion. Adding Nec-1 on day 3 of tissue culture enhanced the islet recovery, proportion of delta cells, beta-cell differentiation and proliferation, and stimulation index. In vivo, this leads to shorter times to normoglycemia, better glycemic control, and higher circulating insulin. Our findings identify the novel time-dependent effects of Nec-1 supplementation on porcine islet quantity and quality prior to transplantation.


Assuntos
Diabetes Mellitus Experimental/terapia , Imidazóis/farmacologia , Indóis/farmacologia , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/efeitos dos fármacos , Técnicas de Cultura de Tecidos/métodos , Animais , Diabetes Mellitus Experimental/metabolismo , Insulina/metabolismo , Ilhotas Pancreáticas/fisiologia , Camundongos Nus , Suínos , Transplante Heterólogo/métodos , Transplantes/efeitos dos fármacos , Transplantes/fisiologia
10.
Medicina (Kaunas) ; 57(8)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34440973

RESUMO

Background and Objectives: Development of hepatitis-B is considered a serious complication after liver transplantation. HBV de novo infection is a rather rare phenomenon, however it deserves attention in the era of donor organ shortage. The aim of the present analysis was to examine its course in liver transplant patients. Materials and Methods: Prevalence of de novo HBV-infections was extracted from our local transplant data base. Analysis focused on the moment of HBV-detection and on the long-term follow-up in terms of biochemical and histological changes over 30 years. Results: 46 patients were identified with the diagnosis of de novo hepatitis B. Median time from liver transplantation to diagnosis was 397 days (7-5505). 39 patients received antiviral therapy. No fibrosis progression could be detected, whereas the grade of inflammation significantly lessened from the moment of HBV detection to the end of histological follow-up over a median of 4344 days (range 123-9490). Patients with a poor virological control demonstrated a significantly poorer overall survival. Conclusions: De novo hepatitis B in liver transplant patients is a condition that can be controlled very well without significant fibrosis progression or graft loss if recognized on time within a regular transplant follow-up schedule.


Assuntos
Hepatite B , Transplante de Fígado , Transplantes , Seguimentos , Hepatite B/epidemiologia , Vírus da Hepatite B , Humanos , Estudos Retrospectivos
11.
Transplant Proc ; 53(6): 1846-1852, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34247860

RESUMO

Although extensive scholarship has been dedicated to the emotional experiences of transplant patients, little is known about the emotional experiences of transplant coordinators. The present article aims to illuminate the phenomenon of emotional labor invested by transplant coordinators. The transplant coordinator is a key person in the process of obtaining consent for organs for transplantation from deceased or living donors. One of the most taxing phenomena among nurses is emotional labor. Emotional labor is a term that denotes the investment of emotional effort to reach a consonance between one's inner authentic feelings and outward expression of one's emotions. Thirteen experienced transplant coordinators were interviewed for the purpose of unveiling their work-related feelings and emotions. Analysis of their narratives revealed 3 types of emotional labor based on the taxonomy proposed by Theodosius: therapeutic, instrumental, and collegial. Findings show that much emotional labor is invested by these nurses. Emotional labor is usually stressful and has an adverse effect on nurses' psychological well-being and health, especially when emotions that are not genuinely felt have to be conveyed. Transplant coordinators must fake their emotional expressions to excel in their job. Their job is psychologically taxing, leading in most cases to regret over choosing this job. Implications for research, policy, and practice include a recommendation that transplant unit managers act to help transplant coordinators avoid the painful emotions that accompany the experience of emotional labor. We provide several useful recommendations about how to alleviate and prevent these negative emotions.


Assuntos
Emoções , Humanos , Obtenção de Tecidos e Órgãos , Transplantes
12.
Sci Rep ; 11(1): 15085, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301975

RESUMO

Many of the > 3.5 million breast cancer survivors in the US have undergone breast reconstruction following mastectomy. Patients report that nipple-areolar complex (NAC) reconstruction is psychologically important, yet current reconstruction techniques commonly result in inadequate shape, symmetry, and nipple projection. Our team has developed an allogeneic acellular graft for NAC reconstruction (dcl-NAC) designed to be easy to engraft, lasting, and aesthetically pleasing. Here, dcl-NAC safety and host-mediated re-cellularization was assessed in a 6-week study in rhesus macaque non-human primates (NHPs). Human-derived dcl-NACs (n = 30) were engrafted on the dorsum of two adult male NHPs with each animal's own nipples as controls (n = 4). Weight, complete blood counts, and metabolites were collected weekly. Grafts were removed at weeks 1, 3, or 6 post-engraftment for histology. The primary analysis evaluated health, re-epithelialization, and re-vascularization. Secondary analysis evaluated re-innervation. Weight, complete blood counts, and metabolites remained mostly within normal ranges. A new epidermal layer was observed to completely cover the dcl-NAC surface at week 6 (13-100% coverage, median 93.3%) with new vasculature comparable to controls at week 3 (p = 0.10). Nerves were identified in 75% of dcl-NACs (n = 9/12) at week 6. These data suggest that dcl-NAC is safe and supports host-mediated re-cellularization.


Assuntos
Produtos Biológicos/uso terapêutico , Mamilos/cirurgia , Retalhos Cirúrgicos/cirurgia , Transplantes/cirurgia , Derme Acelular , Animais , Neoplasias da Mama/cirurgia , Feminino , Humanos , Macaca mulatta , Masculino , Mamoplastia/métodos , Mastectomia/métodos , Modelos Animais , Primatas
13.
Am J Transplant ; 21(10): 3225-3238, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34212485

RESUMO

Although cellular transplantation remains a relatively small field compared to solid organ transplantation, the prospects for advancement in basic science and clinical care remain bountiful. In this review, notable historical events and the current landscape of the field of cellular transplantation are reviewed with an emphasis on islets (allo- and xeno-), hepatocytes (including bioartificial liver), adoptive regulatory immunotherapy, and stem cells (SCs, specifically endogenous organ-specific and mesenchymal). Also, the nascent but rapidly evolving field of three-dimensional bioprinting is highlighted, including its major processing steps and latest achievements. To reach its full potential where cellular transplants are a more viable alternative than solid organ transplants, fundamental change in how the field is regulated and advanced is needed. Greater public and private investment in the development of cellular transplantation is required. Furthermore, consistent with the call of multiple national transplant societies for allo-islet transplants, the oversight of cellular transplants should mirror that of solid organ transplants and not be classified under the unsustainable, outdated model that requires licensing as a drug with the Food and Drug Administration. Cellular transplantation has the potential to bring profound benefit through progress in bioengineering and regenerative medicine, limiting immunosuppression-related toxicity, and providing markedly reduced surgical morbidity.


Assuntos
Diabetes Mellitus Tipo 1 , Transplante das Ilhotas Pancreáticas , Transplantes , Humanos , Tolerância Imunológica , Imunossupressão , Células-Tronco
15.
J Card Surg ; 36(10): 3802-3804, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34309898

RESUMO

Cardiac xenotransplantation is believed to have approached clinical application. However, this approach to advanced heart failure is burdened with a multitude of ethical issues. These issues need to be addressed openly and be broadly discussed in public. Only through an honest and transparent approach, it will be possible to engage the lay audience in the evaluation of pig to human transplant.


Assuntos
Transplante de Coração , Transplantes , Animais , Coração , Xenoenxertos , Suínos , Transplante Heterólogo
16.
Spine (Phila Pa 1976) ; 46(15): E817-E825, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34228692

RESUMO

STUDY DESIGN: Prospective cohort. OBJECTIVE: The aim of this study was to determine the effect of graft type on residual motion and the relationship among residual motion, smoking, and patient-reported outcome (PRO) scores following anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Although most patients develop solid fusion based on static imaging following ACDF, dynamic imaging has revealed that many patients continue to have residual motion at the arthrodesis. METHODS: Forty-eight participants performed dynamic neck flexion/extension and axial rotation within a biplane radiography system 1 year following ACDF (21 one-level, 27 two-level). PRO scores included the Short Form-36, Neck Disability Index, and Cervical Spine Outcomes Questionnaire. An automated model-based tracking process matched subject-specific bone models to the biplane radiographs with sub-millimeter accuracy. Residual motion was measured across the entire arthrodesis site for both one- and two-level fusions in patients who received either allograft or autograft. Patients were divided into "pseudarthrosis" (>3° of flexion/extension residual motion) and "solid fusion" groups. Residual motion and PROs were compared between groups using Student t tests. RESULTS: Patients who received allograft showed more total flexion/extension residual motion (4.1° vs. 2.8°, P = 0.12), although this failed to reach significance. No differences were noted in PROs based on graft type (all P > 0.08) or the presence of pseudarthrosis (all P > 0.13). No differences were noted in residual motion between smokers and nonsmokers (all P > 0.15); however, smokers who received allograft reported worse outcomes than nonsmokers who received allograft and smokers who received autograft. CONCLUSION: Allograft may result in slightly more residual motion at the arthrodesis site 1 year after ACDF. However, there is minimal evidence that PROs are adversely affected by slightly increased residual motion, suggesting that the current definition of pseudarthrosis correlates poorly with clinically significant findings. Additionally, autograft appears to result in superior outcomes in patients who smoke.Level of Evidence: 2.


Assuntos
Vértebras Cervicais/cirurgia , Discotomia , Medidas de Resultados Relatados pelo Paciente , Fusão Vertebral , Discotomia/efeitos adversos , Discotomia/instrumentação , Discotomia/métodos , Humanos , Estudos Prospectivos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos , Transplantes/transplante
17.
Am J Transplant ; 21(7): 2315-2316, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34196485
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