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1.
Soc Sci Med ; 348: 116775, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38579627

RESUMEN

The primary goal of this study is to examine the association between vaccine rhetoric on Twitter and the public's uptake rates of COVID-19 vaccines in the United States, compared to the extent of an association between self-reported vaccine acceptance and the CDC's uptake rates. We downloaded vaccine-related posts on Twitter in real-time daily for 13 months, from October 2021 to September 2022, collecting over half a billion tweets. A previously validated deep-learning algorithm was then applied to (1) filter out irrelevant tweets and (2) group the remaining relevant tweets into pro-, anti-, and neutral vaccine sentiments. Our results indicate that the tweet counts (combining all three sentiments) were significantly correlated with the uptake rates of all stages of COVID-19 shots (p < 0.01). The self-reported level of vaccine acceptance was not correlated with any of the stages of COVID-19 shots (p > 0.05) but with the daily new infection counts. These results suggest that although social media posts on vaccines may not represent the public's opinions, they are aligned with the public's behaviors of accepting vaccines, which is an essential step for developing interventions to increase the uptake rates. In contrast, self-reported vaccine acceptance represents the public's opinions, but these were not correlated with the behaviors of accepting vaccines. These outcomes provide empirical support for the validity of social media analytics for gauging the public's vaccination behaviors and understanding a nuanced perspective of the public's vaccine sentiment for health emergencies.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Autoinforme , Medios de Comunicación Sociales , Medios de Comunicación Sociales/estadística & datos numéricos , Humanos , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Estados Unidos , Vacilación a la Vacunación/estadística & datos numéricos , Vacilación a la Vacunación/psicología , SARS-CoV-2 , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/psicología
2.
Psychiatr Serv ; : appips20230396, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38477837

RESUMEN

OBJECTIVE: This study compared mental health treatment engagement among people with serious mental illness after release from jails that had either a for-profit (N=3 jails) or a nonprofit mental health provider (N=7 jails). METHODS: Across the 10 jails, data were collected in 2019 for 1,238 individuals with serious mental illness. Data included demographic characteristics (age, race-ethnicity, gender, geography, and jail type) and behavioral health variables (previous mental health treatment, psychotropic medication use, substance use, and receipt of jail-based mental health services). Logistic regression was used to predict treatment engagement during the year after release, stratified by type of jail-based mental health provider, in analyses controlled for demographic and behavioral health variables. RESULTS: Almost half (46%, N=573) of the individuals had stayed in jails with a for-profit mental health provider; the other half (54%, N=665) had stayed in jails with a nonprofit provider. In the year after release, 37% (N=458) of all individuals engaged in mental health treatment, and 63% (N=780) did not. Those who had stayed in a jail with a for-profit provider were significantly less likely to engage in mental health treatment during the year after release (AOR=0.59, 95% CI=0.42-0.83, p<0.01), compared with those in jails having a nonprofit provider. CONCLUSIONS: Staying in a jail with a for-profit mental health provider was associated with reduced postrelease engagement with community service providers. Less engagement with services during a pivotal time after release may increase behavioral health crises that erode individuals' well-being and may raise downstream costs due to further criminal legal involvement and emergency care use.

3.
J Mol Cell Cardiol ; 188: 90-104, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38382296

RESUMEN

The role of erythropoietin (EPO) has extended beyond hematopoiesis to include cytoprotection, inotropy, and neurogenesis. Extra-renal EPO has been reported for multiple tissue/cell types, but the physiological relevance remains unknown. Although the EPO receptor is expressed by multiple cardiac cell types and human recombinant EPO increases contractility and confers cytoprotection against injury, whether the heart produces physiologically meaningful amounts of EPO in vivo is unclear. We show a distinct circadian rhythm of cardiac EPO mRNA expression in adult mice and increased mRNA expression during embryogenesis, suggesting physiological relevance to cardiac EPO production throughout life. We then generated constitutive, cardiomyocyte-specific EPO knockout mice driven by the Mlc2v promoter (EPOfl/fl:Mlc2v-cre+/-; EPOΔ/Δ-CM). During cardiogenesis, cardiac EPO mRNA expression and cellular proliferation were reduced in EPOΔ/Δ-CM hearts. However, in adult EPOΔ/Δ- CM mice, total heart weight was preserved through increased cardiomyocyte cross-sectional area, indicating the reduced cellular proliferation was compensated for by cellular hypertrophy. Echocardiography revealed no changes in cardiac dimensions, with modest reductions in ejection fraction, stroke volume, and tachycardia, whereas invasive hemodynamics showed increased cardiac contractility and lusitropy. Paradoxically, EPO mRNA expression in the heart was elevated in adult EPOΔ/Δ-CM, along with increased serum EPO protein content and hematocrit. Using RNA fluorescent in situ hybridization, we found that Epo RNA colocalized with endothelial cells in the hearts of adult EPOΔ/Δ-CM mice, identifying the endothelial cells as a cell responsible for the EPO hyper-expression. Collectively, these data identify the first physiological roles for cardiomyocyte-derived EPO. We have established cardiac EPO mRNA expression is a complex interplay of multiple cell types, where loss of embryonic cardiomyocyte EPO production results in hyper-expression from other cells within the adult heart.


Asunto(s)
Células Endoteliales , Eritropoyetina , Animales , Ratones , Hiperplasia , Hibridación Fluorescente in Situ , Miocitos Cardíacos , ARN , ARN Mensajero/genética
4.
Bioengineering (Basel) ; 10(10)2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37892931

RESUMEN

Acute Liver Failure (ALF) is a life-threatening illness characterized by the rapid onset of abnormal liver biochemistries, coagulopathy, and the development of hepatic encephalopathy. Extracorporeal bioengineered liver (BEL) grafts could offer a bridge therapy to transplant or recovery. The present study describes the manufacture of clinical scale BELs created from decellularized porcine-derived liver extracellular matrix seeded entirely with human cells: human umbilical vein endothelial cells (HUVECs) and primary human liver cells (PHLCs). Decellularized scaffolds seeded entirely with human cells were shown to adhere to stringent sterility and safety guidelines and demonstrated increased functionality when compared to grafts seeded with primary porcine liver cells (PPLCs). BELs with PHLCs were able to clear more ammonia than PPLCs and demonstrated lower perfusion pressures during patency testing. Additionally, to determine the full therapeutic potential of BELs seeded with PHLCs, longer culture periods were assessed to address the logistical constraints associated with manufacturing and transporting a product to a patient. The fully humanized BELs were able to retain their function after cold storage simulating a product transport period. Therefore, this study demonstrates the manufacture of bioengineered liver grafts and their potential in the clinical setting as a treatment for ALF.

5.
J Am Coll Health ; : 1-9, 2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37399569

RESUMEN

Objective: Millions of people use mobile phone or computer-based applications-apps-to maintain their mental health and connect with treatment providers through text- and video-based chat functions. The present study sought to understand young adults' motivations for adopting this technology using the unified theory of acceptance and use of technology (UTAUT), how they use mental health apps, and the gratifications they receive from using mental health apps. Participants: One hundred-eighteen mental health app users responded to an online survey. Methods: A survey was conducted with students at a Midwestern university. The survey included questions regarding current mental health services, mental health apps used, UTAUT and gratifications survey items. Results: A regression analysis suggested users' performance expectancies, effort expectancies, and facilitating conditions predicted the adoption of mental health apps. Young adults most often use mental health apps for stress relief. While they preferred in-person treatment, users described mental health apps as efficient and helpful. Conclusion: Overall, the results reinforce the sense of optimism for the future of mental health apps, suggesting the potential for apps to supplement-but not necessarily replace-in-person care.

6.
bioRxiv ; 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37292919

RESUMEN

Despite the progress made in identifying cellular factors and mechanisms that predict progression and metastasis, breast cancer remains the second leading cause of death for women in the US. Using The Cancer Genome Atlas and mouse models of spontaneous and invasive mammary tumorigenesis, we identified that loss of function of interferon regulatory factor 5 (IRF5) is a predictor of metastasis and survival. Histologic analysis of Irf5 -/- mammary glands revealed expansion of luminal and myoepithelial cells, loss of organized glandular structure, and altered terminal end budding and migration. RNA-seq and ChIP-seq analyses of primary mammary epithelial cells from Irf5 +/+ and Irf5 -/- littermate mice revealed IRF5-mediated transcriptional regulation of proteins involved in ribosomal biogenesis. Using an invasive model of breast cancer lacking Irf5 , we demonstrate that IRF5 re-expression inhibits tumor growth and metastasis via increased trafficking of tumor infiltrating lymphocytes and altered tumor cell protein synthesis. These findings uncover a new function for IRF5 in the regulation of mammary tumorigenesis and metastasis. Highlights: Loss of IRF5 is a predictor of metastasis and survival in breast cancer.IRF5 contributes to the regulation of ribosome biogenesis in mammary epithelial cells.Loss of IRF5 function in mammary epithelial cells leads to increased protein translation.

7.
Int J Offender Ther Comp Criminol ; : 306624X231176015, 2023 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-37269128

RESUMEN

Rural jails are increasingly contributing to the overall jail population and little is known about how they differ from non-rural jails. This study compares demographic, behavioral health and criminal/legal histories of 3,797 individuals who booked into three rural jails and seven non-rural jails. In addition, the study assessed how jails identify mental illness, which was compared to an objective screening instrument (Kessler-6). Individuals in rural jails were more likely to be white, female, have a history of mental health services, misuse substances, and to recidivate. After controlling for these differences, they had 1.5 times greater odds of having a mental illness but lower odds of being identified by the jails. Individuals in rural jails have more behavioral health needs and other criminogenic risk factor and their needs are less likely to be identified by jail staff, which may result in poor connection to diversion or treatment opportunities.

8.
Community Ment Health J ; 59(3): 578-594, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36322279

RESUMEN

The Sequential Intercept Model has helped conceptualize interventions for people with serious mental illness in the criminal/legal system. This paper operationalizes the Sequential Intercept Model into a 35-item scorecard of behavioral health and legal practices. Using interviews, survey, and observational methods, the scorecard assesses an exploratory sample of 19 counties over 27 independent data collections. A series of ordinary least squares regression models assessed the predictor scores on four jail outcomes: prevalence of serious mental illness, length of stay, connections to treatment, and recidivism. Increases in pre-booking scores showed significant decreases in jail prevalence of serious mental illness at the p < 0.05 level, and post-booking scores and overall scores showed significant positive associations with connections to treatment at the p < 0.05 level, though these were non-significant after correcting for multiple comparisons. Preliminary findings suggest a combination of practices across the Sequential Intercept Model could have synergistic impacts on key jail diversion outcomes.


Asunto(s)
Trastornos Mentales , Prisioneros , Psiquiatría , Humanos , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Liderazgo , Derecho Penal
9.
Telemed J E Health ; 29(6): 795-797, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36383108

RESUMEN

The medical environment is on the verge of a dramatic transformation as artificial intelligence (AI) evolves. With the inevitable shift toward AI in health care delivery, there are concerns around its implementation, including ethics, privacy, data representation, and the potential for eliminating physicians. However, AI cannot replicate a physician's knowledge and understanding of the patient as a person and the conditions in which he or she lives. Therefore, provider-patient communication will be paramount in providing safe and effective health care. This piece describes the importance of patient-centered communication and the unintentional move away from this in recent times. We argue that patient-provider communication is vital in the age of AI as it will integrate into the way medicine is practiced, thus leading to more time with the patient to build rapport, trust, and empathy. This will ultimately lead to optimal health-related outcomes.


Asunto(s)
Inteligencia Artificial , Médicos , Femenino , Humanos , Comunicación , Atención a la Salud , Atención Dirigida al Paciente
10.
Telemat Inform ; 76: 101918, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36438457

RESUMEN

The COVID-19 pandemic has demonstrated the importance of large-scale campaigns to facilitate vaccination adherence. Social media presents unique opportunities to reach broader audiences and reduces the costs of conducting national or global campaigns aimed at achieving herd immunity. Nonetheless, few studies have reviewed the effectiveness of prior social media campaigns for vaccination adherence, and several prior studies have shown that social media campaigns do not increase uptake rates. Hence, our objective is to conduct a systematic review to examine the effectiveness of social media campaigns and to identify the reasons for the mixed results of prior studies. Our methodology began with a search of seven databases, which resulted in the identification of 92 interventions conducted over digital media. Out of these 92 studies, only 15 adopted social media campaigns for immunization. We analyzed these 15 studies, along with a coding scheme we developed based on reviews of both health interventions and social media campaigns. Multiple coders, who were knowledgeable about social media campaigns and healthcare, analyzed the 15 cases and obtained an acceptable level of inter-coder reliability (> .80). The results from our systematic review show that only a few social media campaigns have succeeded in enhancing vaccination adherence. In addition, few campaigns have utilized known critical success factors of social media to induce vaccination adherence. Based on these findings, we discuss a set of research questions that informatics scholars should consider when identifying opportunities for using social media to resolve one of the most resilient challenges in public health. Finally, we conclude by discussing how the insights drawn from our systematic reviews contribute to advancing theories, such as social influence and the health belief model, into the realm of social media-based health interventions.

11.
J Hum Nutr Diet ; 36(2): 554-565, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-35320595

RESUMEN

BACKGROUND: Rates of cancer survival are increasing, with more people living with and beyond cancer. Lifestyle recommendations for cancer survivors are based largely on extrapolation from cancer prevention recommendations. This feasibility study was designed to investigate diet and physical activity variables linked to primary prevention and digital behaviour change interventions in cancer survivors and delivered by an oncology dietitian to plan for future research. METHODS: In this 2-month feasibility study, participants who had completed treatment for colorectal cancer were invited to complete online food diaries, underwent physical activity assessment, attended fortnightly telephone consultations with an oncology dietitian and completed an evaluation form. The baseline food diaries were used to help participants pick two lifestyle changes to focus on throughout the intervention. Demographic and clinical data were analysed using descriptive statistics. RESULTS: In total, 996 patients were screened for eligibility; of these, 78 were eligible to approach and 69 were approached, resulting in 20 participants consenting to take part. Overall, the intervention was acceptable with 65% of participants completing an online food diary and 70% engaging with the dietitian over the telephone. The intervention received good feedback, with 100% of those completing the evaluation form reporting they felt supported and found it helpful. CONCLUSIONS: The present study offers preliminary evidence that a lifestyle intervention delivered by an oncology dietitian using digital behaviour change interventions (DBCIs) to cancer survivors is feasible and accepted by participants and providers.


Asunto(s)
Neoplasias Colorrectales , Estilo de Vida , Humanos , Estudios de Factibilidad , Dieta , Ejercicio Físico , Neoplasias Colorrectales/terapia
12.
J Pediatr Health Care ; 37(1): 17-24, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36184375

RESUMEN

INTRODUCTION: A self-guided web site offered by pediatric primary care providers could help parents implement healthy behaviors. METHOD: The Dynamo Kids/¡Niños Dinámicos program was developed with input from parents and health care professionals, creating a bilingual site for parents to learn why and how to implement healthy behavior changes for their children. A single-arm pilot will enroll parents with children 6-12 years with body mass index (BMI) ≥ 85th percentile seen in safety-net practices. Electronic health record modifications alert providers to eligible children at well-child encounters. Consented parents complete online surveys before accessing the site. At 3 months, the providers see children in weight-focused encounters. Outcomes include change in Family Nutrition and Physical Activity parent survey score (primary) and change in child relative BMI (secondary). Additional data include time spent on site, provider surveys, and provider and parent interviews. RESULTS: Pending implementation. DISCUSSION: If program shows promise, a large, controlled study could further evaluate with a goal of broad dissemination.


Asunto(s)
Sobrepeso , Obesidad Infantil , Niño , Humanos , Proyectos Piloto , Obesidad Infantil/epidemiología , Obesidad Infantil/prevención & control , Padres , Índice de Masa Corporal , Atención Primaria de Salud
13.
Am J Physiol Heart Circ Physiol ; 323(6): H1221-H1230, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36331554

RESUMEN

Myocardial ischemic injury and its resolution are the key determinants of morbidity or mortality in heart failure. The cause and duration of ischemia in patients vary. Numerous experimental models and methods have been developed to define genetic, metabolic, molecular, cellular, and pathophysiological mechanisms, in addition to defining structural and functional deterioration of cardiovascular performance. The rapid rise of big data, such as single-cell analysis techniques with bioinformatics, machine learning, and neural networking, brings a new level of sophistication to our understanding of myocardial ischemia. This mini-review explores the multifaceted nature of ischemic injury in the myocardium. We highlight recent state-of-the-art findings and strategies to show new directions of high-impact approach to understanding myocardial tissue remodeling. This next age of heart and circulatory physiology research will be more comprehensive and collaborative to uncover the origin, progression, and manifestation of heart failure while strengthening novel treatment strategies.


Asunto(s)
Insuficiencia Cardíaca , Isquemia Miocárdica , Humanos , Corazón , Miocardio/metabolismo , Isquemia/metabolismo
14.
Life Sci Space Res (Amst) ; 35: 163-169, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36336362

RESUMEN

Implementation of a systematic program for galactic cosmic radiation (GCR) countermeasure discovery will require convenient access to ground-based space radiation analogs. The current gold standard approach for GCR simulation is to use a particle accelerator for sequential irradiation with ion beams representing different GCR components. This has limitations, particularly for studies of non-acute responses, strategies that require robotic instrumentation, or implementation of complex in vitro models that are emerging as alternatives to animal experimentation. Here we explore theoretical and practical issues relating to a different approach to provide a high-LET radiation field for space radiation countermeasure discovery, based on use of compact portable sources to generate neutron-induced charged particles. We present modeling studies showing that DD and DT neutron generators, as well as an AmBe radionuclide-based source, generate charged particles with a linear energy transfer (LET) distribution that, within a range of biological interest extending from about 10 to 200 keV/µm, resembles the LET distribution of reference GCR radiation fields experienced in a spacecraft or on the lunar surface. We also demonstrate the feasibility of using DD neutrons to induce 53BP1 DNA double-strand break repair foci in the HBEC3-KT line of human bronchial epithelial cells, which are widely used for studies of lung carcinogenesis. The neutron-induced foci are larger and more persistent than X ray-induced foci, consistent with the induction of complex, difficult-to-repair DNA damage characteristic of exposure to high-LET (>10 keV/µm) radiation. We discuss limitations of the neutron approach, including low fluence in the low LET range (<10 keV/µm) and the absence of certain long-range features of high charge and energy particle tracks. We present a concept for integration of a compact portable source with a multiplex microfluidic in vitro culture system, and we discuss a pathway for further validation of the use of compact portable sources for countermeasure discovery.


Asunto(s)
Radiación Cósmica , Animales , Humanos , Transferencia Lineal de Energía , Radiación Ionizante , Reparación del ADN , Daño del ADN
15.
Psychol Serv ; 19(4): 621-629, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35389676

RESUMEN

Michigan was one of the first states to feel the effects of the coronavirus disease 2019 (COVID-19) pandemic. This exploratory, mixed-methods study describes 20 county jails' responses to the pandemic across Michigan and presents a case study of one rural jail to examine changes in booking trends and behavioral health needs and services. Qualitatively, jails decreased their population at the outset of the pandemic via early releases, reconsideration of bond, and reductions in arrests. Quantitatively, the greatest prevalence of serious mental illness was found during the spring (initial shutdown period), which had the lowest weekly booking rates. Significant differences were found when comparing charge severity and charge type between study periods. Bookings occurring during the spring were significantly related to felony charges and drug/alcohol charges while individuals were less frequently booked because of violations. Past year recidivism significantly decreased from the winter to summer phase. Policy should mandate that jails screen for behavioral health problems and provide access to behavioral health services, while also expanding diversion opportunities during and after a pandemic. Innovations in continuity of care are critical for both behavioral and public health needs given the high risk for suicide, overdose, and viral spread after release from jail. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Asunto(s)
COVID-19 , Prisioneros , Humanos , Cárceles Locales , Crimen , Servicios de Salud
17.
Adm Policy Ment Health ; 49(1): 104-115, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34272640

RESUMEN

The behavioral health needs, service utilization, and discharge planning provision of veterans in jails have been understudied, yet practitioners must understand each component to ensure veterans' behavioral health needs are met through linkage to culturally-appropriate services. Thus, this study asked: How do veterans differ from non-veterans regarding behavioral health needs, jail-based service engagement, and discharge planning within jails? How do jails identify veterans and are they referred to culturally-appropriate services? In a booking sample across eight jails, this evaluative, cross-sectional study compared veterans to non-veterans by demographics, criminal/legal outcomes, behavioral health needs, and receipt of jail-based behavioral health and discharge planning services. Additionally, the process by which booking officers and jail-based clinicians identify veterans was assessed. Veterans were more likely to be male, older, to have received mental health services prior to their jail stay, and to misuse alcohol. They are less likely to have insecure housing and misuse drugs. No differences existed for length of stay in jail nor recidivism. Veterans were equally likely to receive jail-based behavioral health services, but less likely to receive discharge planning services. While many veterans identified their military status at booking, just over one-third who received services from clinicians were identified as veterans. Of those identified by clinicians, few were referred to culturally-appropriate services as part of their discharge planning. Practitioners in the criminal/legal and mental health systems need to collaborate and develop processes that successfully identify and link veterans to culturally-appropriate services.


Asunto(s)
Trastornos Mentales , Prisioneros , Veteranos , Estudios Transversales , Femenino , Humanos , Cárceles Locales , Masculino , Trastornos Mentales/terapia , Prisiones
18.
Am J Hypertens ; 35(3): 264-271, 2022 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-34605538

RESUMEN

BACKGROUND: The Spontaneously Hypertensive Rat (SHR) Colony was established in 1963 and is the most commonly used rodent model for studying heart failure (HF). Ideally, animal models should recapitulate the clinical disease as closely as possible. Any drift in a genetic model may create a new model that no longer adequately represents the human pathology. Further, instability overtime may lead to conflicting data between laboratories and/or irreproducible results. While systolic blood pressure (SBP) is closely monitored during inbreeding, the sequelae of HF (e.g., cardiac hypertrophy) are not. Thus, the object of this review was to investigate whether the hypertension-induced sequelae of HF in the SHR have remained stable after decades of inbreeding. METHODS: A systematic review was performed to evaluate indices of cardiovascular health in the SHR over the past 60 years. For post hoc statistical analyses, studies were separated into 2 cohorts: Initial (mid to late 1900s) and Current (early 2000s to present) Colony SHRs. Wistar-Kyoto rats (WKY) were used as controls. RESULTS: SBP was consistent between Initial and Current Colony SHRs. However, Current Colony SHRs presented with increased concentric hypertrophy (i.e., elevated heart weight and posterior wall thickness) while cardiac output remained consistent. Since these changes were not observed in the WKY controls, cardiac-derived changes in Current Colony SHRs were unlikely due to differences in environmental conditions. CONCLUSIONS: Together, these data firmly establish a cardiac-based phenotypic shift in the SHR model and provide important insights into the beneficial function of concentric hypertrophy in hypertension-induced HF.


Asunto(s)
Insuficiencia Cardíaca , Hipertensión , Animales , Presión Sanguínea , Cardiomegalia , Insuficiencia Cardíaca/etiología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY
20.
Commun Biol ; 4(1): 1157, 2021 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-34620986

RESUMEN

Organ bioengineering offers a promising solution to the persistent shortage of donor organs. However, the progression of this technology toward clinical use has been hindered by the challenges of reconstituting a functional vascular network, directing the engraftment of specific functional cell types, and defining appropriate culture conditions to concurrently support the health and phenotypic stability of diverse cell lineages. We previously demonstrated the ability to functionally reendothelialize the vasculature of a clinically scaled decellularized liver scaffold with human umbilical vein endothelial cells (HUVECs) and to sustain continuous perfusion in a large animal recovery model. We now report a method for seeding and engrafting primary porcine hepatocytes into a bioengineered liver (BEL) scaffold previously reendothelialized with HUVECs. The resulting BELs were competent for albumin production, ammonia detoxification and urea synthesis, indicating the presence of a functional hepatocyte compartment. BELs additionally slowed ammonia accumulation during in vivo perfusion in a porcine model of surgically induced acute liver failure. Following explant of the graft, BEL parenchyma showed maintenance of canonical endothelial and hepatocyte markers. Taken together, these results support the feasibility of engineering a clinically scaled functional BEL and establish a platform for optimizing the seeding and engraftment of additional liver specific cells.


Asunto(s)
Trasplante de Hígado/métodos , Ingeniería de Tejidos/métodos , Animales , Modelos Animales de Enfermedad , Hepatocitos/trasplante , Células Endoteliales de la Vena Umbilical Humana/trasplante , Humanos , Hígado/cirugía , Fallo Hepático Agudo/cirugía , Perfusión , Sus scrofa/cirugía
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