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1.
J Exp Biol ; 226(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36657384

RESUMO

We investigated how baboons transition from quadrupedal to bipedal walking without any significant interruption in their forward movement (i.e. transition 'on the fly'). Building on basic mechanical principles (momentum only changes when external forces/moments act on the body), insights into possible strategies for such a dynamical mode transition are provided and applied first to the recorded planar kinematics of an example walking sequence (including several continuous quadrupedal, transition and subsequent bipedal steps). Body dynamics are calculated from the kinematics. The strategy used in this worked example boils down to: crouch the hind parts and sprint them underneath the rising body centre of mass. Forward accelerations are not in play. Key characteristics of this transition strategy were extracted: progression speed, hip height, step duration (frequency), foot positioning at touchdown with respect to the hip and the body centre of mass (BCoM), and congruity between the moments of the ground reaction force about the BCoM and the rate of change of the total angular moment. Statistical analyses across the full sample (15 transitions of 10 individuals) confirm this strategy is always used and is shared across individuals. Finally, the costs (in J kg-1 m-1) linked to on the fly transitions were estimated. The costs are approximately double those of both the preceding quadrupedal and subsequent bipedal walking. Given the short duration of the transition as such (<1 s), it is argued that the energetic costs to change walking posture on the fly are negligible when considered in the context of the locomotor repertoire.


Assuntos
Primatas , Caminhada , Animais , Fenômenos Biomecânicos , Fenômenos Mecânicos , Postura , Locomoção , Marcha
2.
Viruses ; 15(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36680230

RESUMO

Microchimerism is the presence of cells in an individual that have originated from a genetically distinct individual. The most common form of microchimerism is fetomaternal microchimerism, i.e., cells from a fetus pass through the placenta and establish cell lineages within the mother. Microchimerism was also described after the transplantation of human organs in human recipients. Consequently, microchimerism may also be expected in xenotransplantation using pig cells or organs. Indeed, microchimerism was described in patients after xenotransplantations as well as in non-human primates after the transplantation of pig organs. Here, for the first time, a comprehensive review of microchimerism in xenotransplantation is given. Since pig cells contain porcine endogenous retroviruses (PERVs) in their genome, the detection of proviral DNA in transplant recipients may be misinterpreted as an infection of the recipient with PERV. To prevent this, methods discriminating between infection and microchimerism are described. This knowledge will be important for the interpretation of screening results in forthcoming human xenotransplantations.


Assuntos
Retrovirus Endógenos , Suínos , Humanos , Animais , Transplante Heterólogo/efeitos adversos , Retrovirus Endógenos/genética , Quimerismo , Primatas , Provírus/genética
3.
Cell ; 186(2): 287-304.e26, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36610399

RESUMO

Whether and how certain transposable elements with viral origins, such as endogenous retroviruses (ERVs) dormant in our genomes, can become awakened and contribute to the aging process is largely unknown. In human senescent cells, we found that HERVK (HML-2), the most recently integrated human ERVs, are unlocked to transcribe viral genes and produce retrovirus-like particles (RVLPs). These HERVK RVLPs constitute a transmissible message to elicit senescence phenotypes in young cells, which can be blocked by neutralizing antibodies. The activation of ERVs was also observed in organs of aged primates and mice as well as in human tissues and serum from the elderly. Their repression alleviates cellular senescence and tissue degeneration and, to some extent, organismal aging. These findings indicate that the resurrection of ERVs is a hallmark and driving force of cellular senescence and tissue aging.


Assuntos
Envelhecimento , Retrovirus Endógenos , Idoso , Animais , Humanos , Camundongos , Envelhecimento/genética , Envelhecimento/patologia , Senescência Celular , Retrovirus Endógenos/genética , Primatas
4.
Hepatol Commun ; 7(2): e0014, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36691970

RESUMO

Pediatric NAFLD has distinct and variable pathology, yet causation remains unclear. We have shown that maternal Western-style diet (mWSD) compared with maternal chow diet (CD) consumption in nonhuman primates produces hepatic injury and steatosis in fetal offspring. Here, we define the role of mWSD and postweaning Western-style diet (pwWSD) exposures on molecular mechanisms linked to NAFLD development in a cohort of 3-year-old juvenile nonhuman primates offspring exposed to maternal CD or mWSD followed by CD or Western-style diet after weaning. We used histologic, transcriptomic, and metabolomic analyses to identify hepatic pathways regulating NAFLD. Offspring exposed to mWSD showed increased hepatic periportal collagen deposition but unchanged hepatic triglyceride levels and body weight. mWSD was associated with a downregulation of gene expression pathways underlying HNF4α activity and protein, and downregulation of antioxidant signaling, mitochondrial biogenesis, and PPAR signaling pathways. In offspring exposed to both mWSD and pwWSD, liver RNA profiles showed upregulation of pathways promoting fibrosis and endoplasmic reticulum stress and increased BiP protein expression with pwWSD. pwWSD increased acylcarnitines and decreased anti-inflammatory fatty acids, which was more pronounced when coupled with mWSD exposure. Further, mWSD shifted liver metabolites towards decreased purine catabolism in favor of synthesis, suggesting a mitochondrial DNA repair response. Our findings demonstrate that 3-year-old offspring exposed to mWSD but weaned to a CD have periportal collagen deposition, with transcriptional and metabolic pathways underlying hepatic oxidative stress, compromised mitochondrial lipid sensing, and decreased antioxidant response. Exposure to pwWSD worsens these phenotypes, triggers endoplasmic reticulum stress, and increases fibrosis. Overall, mWSD exposure is associated with altered expression of candidate genes and metabolites related to NAFLD that persist in juvenile offspring preceding clinical presentation of NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Dieta Ocidental , Antioxidantes , Fibrose , Fenótipo , Primatas
6.
Sci Rep ; 13(1): 82, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596827

RESUMO

In primates, neurons giving rise to the corticospinal tract (CST) are distributed in several motor-related areas of the frontal lobe, such as the primary motor cortex (M1), the supplementary motor area (SMA), and the dorsal and ventral divisions of the premotor cortex (PMd, PMv). Recently, we have shown in macaque monkeys that the morphology of basal dendrites of CST neurons, i.e., large layer V pyramidal neurons, varies among the digit regions of the motor-related areas. Here, we investigated the alterations in basal dendrite morphology of CST neurons after spinal cord injury (SCI). In our monkey model, both the complexity and the spine density of basal dendrites were highly decreased throughout the areas. Notably, these events were less prominent for the PMd than for the M1, SMA, and PMv. In analyzing the density changes post-SCI of the filopodia-, thin-, stubby-, and mushroom-type spines, it was found that the density of filopodia-type spines was increased for all areas, whereas the other types of spines exhibited density decreases. Such spine density reductions were so limited for the PMd as compared to the other areas. The observed plastic changes of CST neurons may contribute to the recovery from impaired motor functions caused by SCI.


Assuntos
Córtex Motor , Traumatismos da Medula Espinal , Animais , Córtex Motor/fisiologia , Macaca , Haplorrinos , Neurônios/fisiologia , Primatas , Células Piramidais , Tratos Piramidais/fisiologia
7.
PLoS Comput Biol ; 19(1): e1010784, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36607933

RESUMO

The relationship between neuronal activity and computations embodied by it remains an open question. We develop a novel methodology that condenses observed neuronal activity into a quantitatively accurate, simple, and interpretable model and validate it on diverse systems and scales from single neurons in C. elegans to fMRI in humans. The model treats neuronal activity as collections of interlocking 1-dimensional trajectories. Despite their simplicity, these models accurately predict future neuronal activity and future decisions made by human participants. Moreover, the structure formed by interconnected trajectories-a scaffold-is closely related to the computational strategy of the system. We use these scaffolds to compare the computational strategy of primates and artificial systems trained on the same task to identify specific conditions under which the artificial agent learns the same strategy as the primate. The computational strategy extracted using our methodology predicts specific errors on novel stimuli. These results show that our methodology is a powerful tool for studying the relationship between computation and neuronal activity across diverse systems.


Assuntos
Caenorhabditis elegans , Modelos Neurológicos , Animais , Humanos , Caenorhabditis elegans/fisiologia , Neurônios/fisiologia , Primatas
8.
Arch Virol ; 168(2): 55, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609605

RESUMO

Porcine cytomegalovirus (PCMV), a porcine roseolovirus (PRV) that is closely related to human herpesviruses 6 and 7, is commonly found in commercial pigs. PCMV/PRV is important in xenotransplantation, because in preclinical trials in which pig organs were transplanted into non-human primates, transmission of PCMV/PRV was shown to be associated with significantly reduced survival of the xenotransplants. PCMV/PRV was also transmitted in the first transplantation of a pig heart into a human patient worldwide and apparently contributed to the death of the patient. The prevalence of PCMV/PRV in wild boars is largely unknown. In this study, we screened wild boars from several areas of northern Italy and Germany to test for the presence of PCMV/PRV using PCR-based and Western blot assays. By Western blot analysis, 54% and 82% of Italian and German wild boars, respectively, were found to be PCMV/PRV positive, while 36% and 60%, respectively, tested positive by real-time polymerase chain reaction (PCR). These data indicate that the virus is common in German and Italian wild boars and that the Western blot assay detected a PCMV/PRV infection more often than did real-time PCR. The data also indicate that pigs raised for xenotransplantation should be protected from contact with materials from wild boars and commercial pigs.


Assuntos
Infecções por Citomegalovirus , Roseolovirus , Doenças dos Suínos , Suínos , Animais , Humanos , Citomegalovirus/genética , Primatas , Reação em Cadeia da Polimerase em Tempo Real , Sus scrofa , Doenças dos Suínos/epidemiologia
9.
Proc Biol Sci ; 290(1990): 20222244, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36629119

RESUMO

How did rhythm originate in humans, and other species? One cross-cultural universal, frequently found in human music, is isochrony: when note onsets repeat regularly like the ticking of a clock. Another universal consists in synchrony (e.g. when individuals coordinate their notes so that they are sung at the same time). An approach to biomusicology focuses on similarities and differences across species, trying to build phylogenies of musical traits. Here we test for the presence of, and a link between, isochrony and synchrony in a non-human animal. We focus on the songs of one of the few singing primates, the lar gibbon (Hylobates lar), extracting temporal features from their solo songs and duets. We show that another ape exhibits one rhythmic feature at the core of human musicality: isochrony. We show that an enhanced call rate overall boosts isochrony, suggesting that respiratory physiological constraints play a role in determining the song's rhythmic structure. However, call rate alone cannot explain the flexible isochrony we witness. Isochrony is plastic and modulated depending on the context of emission: gibbons are more isochronous when duetting than singing solo. We present evidence for rhythmic interaction: we find statistical causality between one individual's note onsets and the co-singer's onsets, and a higher than chance degree of synchrony in the duets. Finally, we find a sex-specific trade-off between individual isochrony and synchrony. Gibbon's plasticity for isochrony and rhythmic overlap may suggest a potential shared selective pressure for interactive vocal displays in singing primates. This pressure may have convergently shaped human and gibbon musicality while acting on a common neural primate substrate. Beyond humans, singing primates are promising models to understand how music and, specifically, a sense of rhythm originated in the primate phylogeny.


Assuntos
Hominidae , Música , Masculino , Animais , Feminino , Humanos , Hylobates/fisiologia , Vocalização Animal/fisiologia , Primatas
10.
Sci Rep ; 13(1): 641, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635347

RESUMO

Global climate changes affect biodiversity and cause species distribution shifts, contractions, and expansions. Climate change and disease are emerging threats to primates, and approximately one-quarter of primates' ranges have temperatures over historical ones. How will climate changes influence Atlantic Forest primate ranges? We used habitat suitability models and measured potential changes in area and distributions shifts. Climate change expected in 2100 may change the distribution area of Atlantic Forest primates. Fourteen species (74%) are predicted to lose more than 50% of their distribution, and nine species (47%) are predicted to lose more than 75% of their distribution. The balance was negative, indicating a potential future loss, and the strength of the reduction in the distribution is related to the severity of climate change (SSP scenarios). Directional shifts were detected to the south. The projected mean centroid latitudinal shift is ~ 51 km to the south for 2100 SSP5-8.5 scenario. The possibility of dispersal will depend on suitable routes and landscape configuration. Greenhouse gas emissions should be urgently reduced. Our results also emphasize that no more forest loss is acceptable in Atlantic Forest, and restoration, canopy bridges, friendly agroecosystems, and monitoring of infrastructure projects are urgent to enable dealing with climate change.


Assuntos
Ecossistema , Florestas , Animais , Biodiversidade , Mudança Climática , Primatas
11.
Nat Ecol Evol ; 7(1): 42-50, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36604552

RESUMO

There is controversy around the mechanisms that guided the change in brain shape during the evolution of modern humans. It has long been held that different cortical areas evolved independently from each other to develop their unique functional specializations. However, some recent studies suggest that high integration between different cortical areas could facilitate the emergence of equally extreme, highly specialized brain functions. Here, we analyse the evolution of brain shape in primates using three-dimensional geometric morphometrics of endocasts. We aim to determine, firstly, whether modern humans present unique developmental patterns of covariation between brain cortical areas; and secondly, whether hominins experienced unusually high rates of evolution in brain covariation as compared to other primates. On the basis of analyses including modern humans and other extant great apes at different developmental stages, we first demonstrate that, unlike our closest living relatives, Homo sapiens retain high levels of covariation between cortical areas into adulthood. Among the other great apes, high levels of covariation are only found in immature individuals. Secondly, at the macro-evolutionary level, our analysis of 400 endocasts, representing 148 extant primate species and 6 fossil hominins, shows that strong covariation between different areas of the brain in H. sapiens and Homo neanderthalensis evolved under distinctly higher evolutionary rates than in any other primate, suggesting that natural selection favoured a greatly integrated brain in both species. These results hold when extinct species are excluded and allometric effects are accounted for. Our findings demonstrate that high covariation in the brain may have played a critical role in the evolution of unique cognitive capacities and complex behaviours in both modern humans and Neanderthals.


Assuntos
Hominidae , Homem de Neandertal , Animais , Humanos , Primatas , Encéfalo , Cabeça
12.
Sci Adv ; 9(2): eadd4623, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36630502

RESUMO

Lipid nanoparticle (LNP)-based mRNA delivery holds promise for the treatment of inherited retinal degenerations. Currently, LNP-mediated mRNA delivery is restricted to the retinal pigment epithelium (RPE) and Müller glia. LNPs must overcome ocular barriers to transfect neuronal cells critical for visual phototransduction, the photoreceptors (PRs). We used a combinatorial M13 bacteriophage-based heptameric peptide phage display library for the mining of peptide ligands that target PRs. We identified the most promising peptide candidates resulting from in vivo biopanning. Dye-conjugated peptides showed rapid localization to the PRs. LNPs decorated with the top-performing peptide ligands delivered mRNA to the PRs, RPE, and Müller glia in mice. This distribution translated to the nonhuman primate eye, wherein robust protein expression was observed in the PRs, Müller glia, and RPE. Overall, we have developed peptide-conjugated LNPs that can enable mRNA delivery to the neural retina, expanding the utility of LNP-mRNA therapies for inherited blindness.


Assuntos
Nanopartículas , Roedores , Camundongos , Animais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ligantes , Retina/metabolismo , Peptídeos/metabolismo , Primatas
13.
PeerJ ; 11: e14523, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36650833

RESUMO

Cusp patterning on living and extinct primate molar teeth plays a crucial role in species diagnoses, phylogenetic inference, and the reconstruction of the evolutionary history of the primate clade. These studies rely on a system of nomenclature that can accurately identify and distinguish between the various structures of the crown surface. However, studies at the enamel-dentine junction (EDJ) of some primate taxa have demonstrated a greater degree of cusp variation and expression at the crown surface than current systems of nomenclature allow. In this study, we review the current nomenclature and its applicability across all the major primate clades based on investigations of mandibular crown morphology at the enamel-dentine junction revealed through microtomography. From these observations, we reveal numerous new patterns of lower molar accessory cusp expression in primates. We highlight numerous discrepancies between the expected patterns of variation inferred from the current academic literature, and the new patterns of expected variation seen in this study. Based on the current issues associated with the crown nomenclature, and an incomplete understanding of the precise developmental processes associated with each individual crown feature, we introduce these structures within a conservative, non-homologous naming scheme that focuses on simple location-based categorisations. Until there is a better insight into the developmental and phylogenetic origin of these crown features, these categorisations are the most practical way of addressing these structures. Until then, we also suggest the cautious use of accessory cusps for studies of taxonomy and phylogeny.


Assuntos
Coroa do Dente , Dente , Animais , Filogenia , Primatas , Dente Molar/anatomia & histologia
14.
Antiviral Res ; 210: 105522, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36592667

RESUMO

In 1998, Mike Bray and colleagues published the first immunocompetent laboratory mouse model of Ebola virus disease. Often labeled by peer reviewers as inferior to large nonhuman primate efforts, this model initially laid the foundation for the recent establishment of panel-derived cross-bred and humanized mouse models and a golden hamster model. Nonhuman primate research has always been associated with ethical concerns and is sometimes deemed scientifically questionable due to the necessarily low animal numbers in individual studies. Independent of these concerns, the now-global severe shortage of commercially available large nonhuman primates may pragmatically push research toward increased and improved rodent modeling that may altogether replace nonhuman primate studies in the short term as well as in an optimal future.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola , Cricetinae , Animais , Camundongos , Primatas , Mesocricetus , Modelos Animais de Doenças
15.
J Neural Eng ; 20(1)2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36603218

RESUMO

Objective:The main objective of this study was to induce and evaluate drug-dose-dependent outer retinal degeneration in cynomolgus monkeys by application of N-methyl-N-nitrosourea (MNU).Approach:Intravitreal temporary tamponade induced outer retinal degeneration with MNU solutions (2-3 mg ml-1) after vitrectomy in five cynomolgus monkeys. Optical coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinography (ffERG), and visual evoked potentials (VEP) were performed at baseline and weeks 2, 6, and 12 postoperatively. At week 12, OCT angiography, histology, and immunohistochemistry were performed.Main results:Outer retinal degeneration was observed in four monkeys, especially in the peripheral retina. Anatomical and functional changes occurred at week 2 and persisted until week 12. FAF images showed hypoautofluorescence dots, similar to AF patterns seen in human retinitis pigmentosa. Hyperautofluorescent lesions in the pericentral area were also observed, which corresponded to the loss of the ellipsoid zone on OCT images. OCT revealed thinning of the outer retinal layer adding to the loss of the ellipsoid zone outside the vascular arcade. Histological findings confirmed that the abovementioned changes resulted from a gradual loss of photoreceptors from the perifovea to the peripheral retina. In contrast, the inner retina, including ganglion cell layers, was preserved. Functionally, a decrease or extinction of scotopic ffERGs was observed, which indicated rod-dominant loss. Nevertheless, VEPs were relatively preserved.Significance:Therefore, we can conclude that temporary exposure to intravitreal MNU tamponade after vitrectomy induces rod-dominant outer retinal degeneration in cynomolgus monkeys, especially in the peripheral retina.


Assuntos
Degeneração Retiniana , Animais , Macaca fascicularis , Metilnitrosoureia/efeitos adversos , Potenciais Evocados Visuais , Retina/patologia , Primatas , Tomografia de Coerência Óptica/métodos
16.
Genes (Basel) ; 14(1)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36672969

RESUMO

The gut microbiome plays a vital role in host ecological adaptation, especially dietary adaptations. Primates have evolved a variety of dietary and gut physiological structures that are useful to explore the role of the gut microbiome in host dietary adaptations. Here, we characterize gut microbiome transcriptional activity in ten fecal samples from primates with three different diets and compare the results to their previously reported metagenomic profile. Bacteria related to cellulose degradation, like Bacteroidaceae and Alcaligenaceae, were enriched and actively expressed in the gut microbiome of folivorous primates, and functional analysis revealed that the glycan biosynthesis and metabolic pathways were significantly active. In omnivorous primates, Helicobacteraceae, which promote lipid metabolism, were significantly enriched in expression, and activity and xenobiotic biodegradation and metabolism as well as lipid metabolism pathways were significantly active. In frugivorous primates, the abundance and activity of Elusimicrobiaceae, Neisseriaceae, and Succinivibrionaceae, which are associated with digestion of pectin and fructose, were significantly elevated, and the functional pathways involved in the endocrine system were significantly enriched. In conclusion, the gut microbiome contributes to host dietary adaptation by helping hosts digest the inaccessible nutrients in their specific diets.


Assuntos
Microbioma Gastrointestinal , Animais , Microbioma Gastrointestinal/genética , Primatas/genética , Dieta , Bactérias/metabolismo , Fezes/microbiologia
17.
Neurobiol Dis ; 176: 105945, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36481436

RESUMO

Degeneration of neurons and circuits across the striatum shows stereotyped time-course and spatial topography patterns that are distinct for Huntington's disease, Parkinson's disease, or the Tauopathies. These patterns of neurodegeneration in humans have not yet been systematically related to developmental, connectional, cellular, and chemical factors studied in human and non-human primates, that may underlie potential differences in selective vulnerability across striatal sectors. Relating primate anatomy to human pathology could provide new venues for identifying molecular, cellular, and connectional factors linked to the degeneration of striatal neurons and circuits. This review describes and summarizes several developmental, cellular, structural, and connectional features of the primate striatum in relation to patterns of neurodegeneration in the striatum of humans and of non-human primate models. We review (1) the types of neurons in the primate striatum, (2) the cyto-, myelo-, and chemoarchitecture of the primate striatum, (3) the developmental origin of the striatum in light of modern patterning studies, (4) the organization of corticostriatal projections in relation to cortical types, and (5) the topography and time-course of neuron loss, glial reaction, and protein aggregation induced by neurodegenerative diseases in humans and in non-human primate models across striatal sectors and their corresponding cortical areas. We summarize current knowledge about key aspects of primate striatal anatomy and human pathology and indicate knowledge gaps that should be addressed in future studies. We aim to identify factors for selective vulnerability to neurodegeneration of striatal neurons and circuits and obtain hints that could help elucidate striatal pathology in humans.


Assuntos
Doença de Huntington , Neostriado , Animais , Humanos , Neostriado/patologia , Corpo Estriado/patologia , Primatas/fisiologia , Neurônios/metabolismo , Doença de Huntington/metabolismo , Vias Neurais/patologia
18.
Vaccine ; 41(3): 836-843, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36564277

RESUMO

Yellow fever vaccine associated neurovirulence and viscerotropism have been reported by various countries. In this study, the neurovirulence, viscerotropism and immunogenicity of yellow fever vaccine seed lots (master and working) and final product manufactured at Serum Institute of India (SII) were evaluated in cynomolgus monkeys. WHO reference virus 168-73 and Stamaril™ as a control vaccine was used for comparison. Neurovirulence and viscerotropism scores of the seed lots and final product were lower than Stamaril™. The SII seed virus and vaccine complies to the WHO requirement for neurovirulence, viscerotropism and immunogenicity, when tested in comparison to WHO reference seed virus 168/73. All challenged animals showed 100 % seroconversion as early as day 14 and neutralizing antibody titers were sustainable at day 30 in all animals.


Assuntos
Vacina contra Febre Amarela , Febre Amarela , Animais , Vírus da Febre Amarela , Febre Amarela/prevenção & controle , Primatas , Antígenos Virais , Vacinas Atenuadas
19.
20.
Hum Immunol ; 84(1): 1-4, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36529614

RESUMO

The application of xenotransplantation of porcine organs and tissues for treatment of disease, sought for more than a century, might soon be realized. Until now, the immune response of recipients against xenogeneic organs and tissues posed the main obstacle to clinical application. However, decades of research into this immune response and identification of other molecular barriers together with advances in genetic engineering and cloning of large animals and immune therapeutics coalesced to support prolonged survival and function of porcine organ grafts in nonhuman primates. This experimental progress in turn sparks consideration of clinical trials. The papers in this special section provide authoritative views concerning the immune hurdles that still limit and potentially still preclude clinical application of xenotransplantation. Xenoreactive antibodies elicited in T cell-dependent B cell-responses constitute the most important hurdle and control of these responses impels use of intense regimens of immunosuppression. These antibodies pose a danger to xenografts and potentially compromise subsequent allografts. However, new insights into the specificity of these antibodies, the pathways and kinetics of production and genetic determinants of pathogenicity offer novel opportunities for intervention. Likewise, the rapid ability to propose and test new strategies in nonhuman primate models hastens needed advances. However further progress will depend on development and validation of laboratory methods for identification and assay of pathogenic immune responses and evaluation of the response to therapy.


Assuntos
Engenharia Genética , Primatas , Humanos , Animais , Suínos , Transplante Heterólogo , Tolerância Imunológica , Xenoenxertos , Anticorpos , Rejeição de Enxerto
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