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Platelet lysate, derived from platelets, are valuable biological products rich in bioactive molecules. Their use promotes tissue healing and modulates inflammation. However, maintaining the stability and bioactivity of platelet lysate is challenging since they degrade rapidly at room temperature. This study focused on the possibility to confer enhanced stability to freeze-dried equine platelet lysate as an alternative to platelet-rich plasma (PRP). Platelet lysate (PL) was derived from PRP and freeze-dried either as such or using various adjuvants. Primary cell cultures of porcine Vascular Wall-Mesenchymal Stem Cells were treated with different PL formulations, and cell viability was assessed using an MTT assay. Overall, the addition of PL significantly improved cell viability as compared to controls without growth factor supplementation or with foetal bovine serum. Notably, the freeze-drying process maintained the effectiveness of the PL for at least a week. Furthermore, the study revealed that varying the horse as the source of PL could yield varying effects on cell viability. Detailed freeze-drying protocols were established, including freezing, primary drying and secondary drying phases, and the type of adjuvant. This study demonstrated the potential of freeze-dried equine PL as a viable alternative to PRP and highlighted the importance of precise freeze-drying protocols and adjuvants for standardization. Equine PL showed promise for medical treatment in horses, offering advantages such as extended shelf life, ease of handling, and reduced transportation costs, with the potential for broadened therapeutic usage.

Machine perfused ex-vivo organs offer an excellent experimental platform, e.g., for studying organ physiology and for conducting pre-clinical trials for drug delivery. One main challenge in machine perfusion is the accurate assessment of organ condition. Assessment is often performed using viability markers, i.e., lactate concentrations and blood gas analysis. Nonetheless, existing markers for condition assessment can be inconclusive, and novel assessment methods remain of interest. Over the last decades, several imaging modalities have given unique insights into the assessment of organ condition. A systematic review was conducted according to accepted guidelines to evaluate these medical imaging methods, focussed on literature that use machine perfused human-sized organs, that determine organ condition with medical imaging. A total of 18 out of 1,465 studies were included that reported organ condition results in perfused hearts, kidneys, and livers, using both conventional viability markers and medical imaging. Laser speckle imaging, ultrasound, computed tomography, and magnetic resonance imaging were used to identify local ischemic regions and quantify intraorgan perfusion. A detailed investigation of metabolic activity was achieved using 31P magnetic resonance imaging and near-infrared spectroscopy. The current review shows that medical imaging is a powerful tool to assess organ condition. [ABSTRACT FROM AUTHOR]

Neoplastic processes of the mandible and their treatment are rarely reported in large animal species. Specifically, giant cell tumor of bone is an uncommon tumor in animals and has been associated in humans with locally invasive behavior and a high recurrence rate. En-bloc resection is the treatment of choice, but depending on the localization of the tumor, this may result in functional deficits. This report details the diagnostic work-up, treatment, and long-term outcome of a giant cell tumor of bone involving the rostral mandible and mandibular symphysis of a goat. Extensive rostral mandibulectomy involving the entire mandibular symphysis without surgical fixation of the hemimandibles was performed. Histological and electron microscopic findings of the tumor were consistent with a giant cell tumor of bone. Although a mutation of the H3F3A gene is considered the driver of tumor development in human giant cell tumors, using molecular analysis, this gene mutation could not be confirmed in this case. Follow-up examinations revealed spontaneous secondary fusion of both hemimandibles and no signs of tumor recurrence. Nearly 1 year after surgery, the owners reported no signs of tumor regrowth. [ABSTRACT FROM AUTHOR]

Purpose: To assess the safety and feasibility of direct vitrectomy-sparing subretinal injection for gene delivery in a large animal model. Methods: The experimental Liběchov minipigs were used for subretinal delivery of a plasmid DNA vector (pS/MAR-CMV-copGFP) with cytomegalovirus (CMV) promoter, green fluorescent protein (GFP) reporter (copGFP) and a scaffold/matrix attachment region (S/MAR) sequence. The eyes were randomized to subretinal injection of the vector following pars plana vitrectomy (control group) or a direct injection without prior vitrectomy surgery (experimental group). Intra- and post-operative observations up to 30 days after surgery were compared. Results: Six eyes of three mini-pigs underwent surgery for delivery into the subretinal space. Two eyes in the control group were operated with a classical approach (lens-sparing vitrectomy and posterior hyaloid detachment). The other four eyes in the experimental group were injected directly with a subretinal cannula without vitrectomy surgery. No adverse events, such as endophthalmitis, retinal detachment and intraocular pressure elevation were observed post-operatively. The eyes in the experimental group had both shorter surgical time and recovery while achieving the same surgical goal. Conclusions: This pilot study demonstrates that successful subretinal delivery of gene therapy vectors is achievable using a direct injection without prior vitrectomy surgery. [ABSTRACT FROM AUTHOR]

Freshwater megafauna, such as sturgeons, giant catfishes, river dolphins, hippopotami, crocodylians, large turtles, and giant salamanders, have experienced severe population declines and range contractions worldwide. Although there is an increasing number of studies investigating the causes of megafauna losses in fresh waters, little attention has been paid to synthesising the impacts of megafauna on the abiotic environment and other organisms in freshwater ecosystems, and hence the consequences of losing these species. This limited understanding may impede the development of policies and actions for their conservation and restoration. In this review, we synthesise how megafauna shape ecological processes in freshwater ecosystems and discuss their potential for enhancing ecosystem restoration. Through activities such as movement, burrowing, and dam and nest building, megafauna have a profound influence on the extent of water bodies, flow dynamics, and the physical structure of shorelines and substrata, increasing habitat heterogeneity. They enhance nutrient cycling within fresh waters, and cross‐ecosystem flows of material, through foraging and reproduction activities. Freshwater megafauna are highly connected to other freshwater organisms via direct consumption of species at different trophic levels, indirect trophic cascades, and through their influence on habitat structure. The literature documenting the ecological impacts of freshwater megafauna is not evenly distributed among species, regions, and types of ecological impacts, with a lack of quantitative evidence for large fish, crocodylians, and turtles in the Global South and their impacts on nutrient flows and food‐web structure. In addition, population decline, range contraction, and the loss of large individuals have reduced the extent and magnitude of megafaunal impacts in freshwater ecosystems, rendering a posteriori evaluation more difficult. We propose that reinstating freshwater megafauna populations holds the potential for restoring key ecological processes such as disturbances, trophic cascades, and species dispersal, which will, in turn, promote overall biodiversity and enhance nature's contributions to people. Challenges for restoration actions include the shifting baseline syndrome, potential human–megafauna competition for habitats and resources, damage to property, and risk to human life. The current lack of historical baselines for natural distributions and population sizes of freshwater megafauna, their life history, trophic interactions with other freshwater species, and interactions with humans necessitates further investigation. Addressing these knowledge gaps will improve our understanding of the ecological roles of freshwater megafauna and support their full potential for facilitating the development of effective conservation and restoration strategies to achieve the coexistence of humans and megafauna. [ABSTRACT FROM AUTHOR]

Scaffold-guided breast tissue regeneration (SGBTR) can transform both reconstructive and cosmetic breast surgery. Implant-based surgery is the most common method. However, there are inherent limitations, as it involves replacement of tissue rather than regeneration. Regenerating autologous soft tissue has the potential to provide a more like-for-like reconstruction with minimal morbidity. Our SGBTR approach regenerates soft tissue by implanting additively manufactured bioresorbable scaffolds filled with autologous fat graft. A pre-clinical large animal study was conducted by implanting 100 mL breast scaffolds (n = 55) made from medical-grade polycaprolactone into 11 minipigs for 12 months. Various treatment groups were investigated where immediate or delayed autologous fat graft, as well as platelet rich plasma, were added to the scaffolds. Computed tomography and magnetic resonance imaging were performed on explanted scaffolds to determine the volume and distribution of the regenerated tissue. Histological analysis was performed to confirm the tissue type. At 12 months, we were able to regenerate and sustain a mean soft tissue volume of 60.9 ± 4.5 mL (95% CI) across all treatment groups. There was no evidence of capsule formation. There were no immediate or long-term post-operative complications. In conclusion, we were able to regenerate clinically relevant soft tissue volumes utilizing SGBTR in a pre-clinical large animal model. [ABSTRACT FROM AUTHOR]

Neoplastic processes of the mandible and their treatment are rarely reported in large animal species. Specifically, giant cell tumor of bone is an uncommon tumor in animals and has been associated in humans with locally invasive behavior and a high recurrence rate. En-bloc resection is the treatment of choice, but depending on the localization of the tumor, this may result in functional deficits. This report details the diagnostic work-up, treatment, and long-term outcome of a giant cell tumor of bone involving the rostral mandible and mandibular symphysis of a goat. Extensive rostral mandibulectomy involving the entire mandibular symphysis without surgical fixation of the hemimandibles was performed. Histological and electron microscopic findings of the tumor were consistent with a giant cell tumor of bone. Although a mutation of the H3F3A gene is considered the driver of tumor development in human giant cell tumors, using molecular analysis, this gene mutation could not be confirmed in this case. Follow-up examinations revealed spontaneous secondary fusion of both hemimandibles and no signs of tumor recurrence. Nearly 1 year after surgery, the owners reported no signs of tumor regrowth.

Abstract Background Mucopolysaccharidosis IIIC (MPSIIIC) is one of four Sanfilippo diseases sharing clinical symptoms of severe cognitive decline and shortened lifespan. The missing enzyme, heparan sulfate acetyl-CoA: α-glucosaminide-N-acetyltransferase (HGSNAT), is bound to the lysosomal membrane, therefore cannot cross the blood-brain barrier or diffuse between cells. We previously demonstrated disease correction in MPSIIIC mice using an Adeno-Associated Vector (AAV) delivering HGSNAT via intraparenchymal brain injections using an AAV2 derived AAV-truetype (AAV-TT) serotype with improved distribution over AAV9. Methods Here, intraparenchymal AAV was delivered in sheep using catheters or Hamilton syringes, placed using Brainlab cranial navigation for convection enhanced delivery, to reduce proximal vector expression and improve spread. Results Hamilton syringes gave improved AAV-GFP distribution, despite lower vector doses and titres. AAV-TT-GFP displayed moderately better transduction compared to AAV9-GFP but both serotypes almost exclusively transduced neurons. Functional HGSNAT enzyme was detected in 24-37% of a 140g gyrencephalic sheep brain using AAV9-HGSNAT with three injections in one hemisphere. Conclusions Despite variabilities in volume and titre, catheter design may be critical for efficient brain delivery. These data help inform a clinical trial for MPSIIIC.

Sensorineural hearing loss (SNHL), caused by pathology in the cochlea, is the most common type of hearing loss in humans. It is generally irreversible with very few effective pharmacological treatments available to prevent the degenerative changes or minimise the impact. Part of this has been attributed to difficulty of translating "proof-of-concept" for novel treatments established in small animal models to human therapies. There is an increasing interest in the use of sheep as a large animal model. In this article, we review the small and large animal models used in pre-clinical hearing research such as mice, rats, chinchilla, guinea pig, rabbit, cat, monkey, dog, pig, and sheep to humans, and compare the physiology, inner ear anatomy, and some of their use as model systems for SNHL, including cochlear implantation surgeries. Sheep have similar cochlear anatomy, auditory threshold, neonatal auditory system development, adult and infant body size, and number of birth as humans. Based on these comparisons, we suggest that sheep are well-suited as a potential translational animal model that bridges the gap between rodent model research to the clinical use in humans. This is especially in areas looking at changes across the life-course or in specific areas of experimental investigation such as cochlear implantation and other surgical procedures, biomedical device development and age-related sensorineural hearing loss research. Combined use of small animals for research that require higher throughput and genetic modification and large animals for medical translation could greatly accelerate the overall translation of basic research in the field of auditory neuroscience from bench to clinic. [ABSTRACT FROM AUTHOR]

Objective: Determine the association of time of day, day of week, time of year, holiday, and phase of moon on academic ambulatory and hospital emergency caseload for equine and food animal species. Design: Retrospective study. Setting: Large animal teaching hospital emergency service. Animals: Equine and food animals. Interventions: None. Measurements and Main Results: The hospital database was searched for after‐hours on‐farm and in‐hospital emergencies seen from 2014 to 2020. Variables included date and time of admission, species (equine or food/fiber animal [FA]), and hospital service (field or in‐hospital). The association of the caseload with time of day, day of week, day of year (holiday, full moon, or new moon), and season of year was defined and examined. The majority of equine field‐based emergencies occurred on the weekend, in contrast to 44.8% of hospital cases. Most equine emergencies occurred between 4:00 p.m. and midnight on weekdays and between 8:00 a.m. and 4:00 p.m. on weekends for both field (89.1% and 46.9%) and hospital (82.8% and 48%) services. The same was true for FA cases on the farm (90% and 49.2%) and in the hospital (85% and 51.4%). More equine cases (67%) were seen in the field than FA. Winter had the fewest emergency cases for all species and locations, and spring had the most for FA. The majority of holiday equine emergencies were seen in the field (62.2%), but the majority of holiday FA emergencies were seen in the hospital (66.3%). Moon phase had no significance on caseload for all species and locations. Conclusions: Saturdays and Sundays were the busiest days for all species and services. Winter was the slowest time for emergencies for all species and services. Most emergencies were seen between 4:00 p.m. and midnight on weekdays and between 8:00 a.m. and 4:00 p.m. on Sundays and Saturdays. [ABSTRACT FROM AUTHOR]

This perspective summarizes the genesis, development, and potential future directions of the multispecies JOR Spine histopathology series.

Hydrodynamics-based gene transfer has been successfully employed for in vivo gene delivery to the liver of small animals by tail vein injection and of large animals using a computer-assisted and image-guided protocol. In an effort to develop a hydrodynamic gene delivery procedure clinically applicable for gene therapy, we have evaluated the safety and effectiveness of a lobe-specific hydrodynamic delivery procedure for hepatic gene delivery in baboons. Reporter plasmid was used to assess the gene delivery efficiency of the lobe-specific hydrodynamic gene delivery, and plasmid-carrying human factor IX gene was used to examine the pattern of long-term gene expression. The results demonstrated liver lobe-specific gene delivery, therapeutic levels of human factor IX gene expression lasting for >100 days, and the efficacy of repeated hydrodynamic gene delivery into the same liver lobes. Other than a transient increase in blood concentration of liver enzymes right after the injection, no significant adverse events were observed in animals during the study period. The results obtained from this first non-human primate study support the clinical applicability of the procedure for lobe-specific hydrodynamic gene delivery to liver.

In recent decades, the pig has attracted considerable attention as an important intermediary model animal in translational biobehavioral research due to major similarities between pig and human neuroanatomy, physiology, and behavior. As a result, there is growing interest in using pigs to model many human neurological conditions and injuries. Pigs are highly intelligent and are capable of performing a wide range of behaviors, which can provide valuable insight into the effects of various neurological disease states. One area in which the pig has emerged as a particularly relevant model species is in the realm of neurotrauma research. Indeed, the number of investigators developing injury models and assessing treatment options in pigs is ever-expanding. In this review, we examine the use of pigs for cognitive and behavioral research as well as some commonly used physiological assessment methods. We also discuss the current usage of pigs as a model for the study of traumatic brain injury. We conclude that the pig is a valuable animal species for studying cognition and the physiological effect of disease, and it has the potential to contribute to the development of new treatments and therapies for human neurological and psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background: Mucopolysaccharidosis IIIC (MPSIIIC) is one of four Sanfilippo diseases sharing clinical symptoms of severe cognitive decline and shortened lifespan. The missing enzyme, heparan sulfate acetyl-CoA: α-glucosaminide-N-acetyltransferase (HGSNAT), is bound to the lysosomal membrane, therefore cannot cross the blood-brain barrier or diffuse between cells. We previously demonstrated disease correction in MPSIIIC mice using an Adeno-Associated Vector (AAV) delivering HGSNAT via intraparenchymal brain injections using an AAV2 derived AAV-truetype (AAV-TT) serotype with improved distribution over AAV9. Methods: Here, intraparenchymal AAV was delivered in sheep using catheters or Hamilton syringes, placed using Brainlab cranial navigation for convection enhanced delivery, to reduce proximal vector expression and improve spread. Results: Hamilton syringes gave improved AAV-GFP distribution, despite lower vector doses and titres. AAV-TT-GFP displayed moderately better transduction compared to AAV9-GFP but both serotypes almost exclusively transduced neurons. Functional HGSNAT enzyme was detected in 24-37% of a 140g gyrencephalic sheep brain using AAV9-HGSNAT with three injections in one hemisphere. Conclusions: Despite variabilities in volume and titre, catheter design may be critical for efficient brain delivery. These data help inform a clinical trial for MPSIIIC. [ABSTRACT FROM AUTHOR]

Veterinary hospitals are important locations for various sick and immunocompromised animal patients. These centers may act as reservoirs for nosocomial diseases such as Salmonella infection, one of the most common causes of healthcare-associated infections in veterinary hospitals. The study was performed at the Large Animal Ward (LAW), University Veterinary Hospital, Universiti Putra Malaysia, to assess the environment's degree of Salmonella spp. contamination. Environmental samples were obtained from various floor and surface areas in the LAW using sterile, moistened gauze. Salmonella spp. was determined using conventional bacteriological culture on all samples. Positive Salmonella isolates were subject to antimicrobial sensitivity testing. A total of 6 out of 135 (4.4%) samples were found to be positive for Salmonella spp., with 5/116 (4.3%) samples obtained from the ward environment and 1/19 (5.3%) obtained from reusable equipment. Antimicrobial sensitivity testing revealed three resistance profiles: all isolates were resistant to penicillin and enrofloxacin, one isolate was resistant to streptomycin, and one was resistant to gentamicin. The results indicate that animal treatment areas within the LAW can become contaminated with Salmonella spp. This study highlights the importance of improving biosecurity programs to prevent nosocomial diseases in patients and the hospital environment. [ABSTRACT FROM AUTHOR]

Purpose of Review: Heart failure leads to high mortality. The failing myocardium cannot often be rescued as heart regeneration is mostly compromised by disease progress. Stem cell therapy is a strategy under development to replace the impaired myocardium for recovery after heart injury. Recent Findings: Many studies have provided evidence of the beneficial effects of pluripotent stem cell-derived cardiomyocyte (CM) implantation into diseased rodent hearts, but there are still many challenges and limitations to replicating the same effects in large animal models for preclinical validation. Summary: In this review, we summarize progress in the use of pluripotent stem cell-derived CMs in large animal models based on three key parameters: species selection, cell source, and delivery. Most importantly, we discuss the current limitations and challenges that need to be solved to advance this technology to the translational stage. [ABSTRACT FROM AUTHOR]

Animal models are important for understanding the pathogenesis of human diseases and for developing and testing new drugs. Pigs have been widely used in the research on the cardiovascular, skin barrier, gastrointestinal, and central nervous systems as well as organ transplantation. Recently, pigs also become an attractive large animal model for the study of neurodegenerative diseases because their brains are very similar to human brains in terms of mass, gully pattern, vascularization, and the proportions of the gray and white matters. Although adeno-associated virus type 9 (AAV9) has been widely used to deliver transgenes in the brain, its utilization in large animal models remains to be fully characterized. Here, we report that intravenous injection of AAV9-GFP can lead to widespread expression of transgene in various organs in the pig. Importantly, GFP was highly expressed in various brain regions, especially the striatum, cortex, cerebellum, hippocampus, without detectable inflammatory responses. These results suggest that intravenous AAV9 administration can be used to establish large animal models of neurodegenerative diseases caused by gene mutations and to treat these animal models as well.

Simple Summary: This study was designed to better understand the mental health of U.S. swine veterinarians who were involved in the mass depopulation events related to COVID-19. A total of 25 swine veterinarians, participants from a larger quantitative study, volunteered to be interviewed about their experiences related to the COVID-19 mass depopulation event. The themes that arose from these interviews included: (1) the need to be better prepared for crisis events; (2) lack of public understanding; (3) moral distress; (4) empathy for others, especially young veterinarians; (5) sources of support; (6) pride, honor and gratitude; and (7) an overarching theme of emotional distancing and detachment—concerns external to one's own mental health. Based on these results, we recommend additional training and supportive services for those who might be involved in future depopulation efforts. This qualitative study (n = 25) was created to better understand the mental health of U.S. swine veterinarians who were involved in the mass depopulation events related to COVID-19. A total of 25 swine veterinarians, participants in a previous larger quantitative study, volunteered to be interviewed about their experiences related to the COVID-19 mass depopulation event. Themes that emerged from these interviews included: (1) the need to be better prepared for crisis events; (2) lack of public understanding; (3) moral distress; (4) empathy for others, especially young veterinarians; (5) sources of support; (6) pride, honor and gratitude; and (7) an overarching theme of emotional distancing and detachment—concerns external to one's own mental health. Based on our results, we recommend additional training and supportive services for those who might be involved in future depopulation efforts. Additionally, we suggest that the veterinary profession prioritize public education campaigns to help the public better understand the need for depopulation. [ABSTRACT FROM AUTHOR]

IntroductionFacial expression scoring has proven to be useful for pain evaluation in humans. In the last decade, equivalent scales have been developed for various animal species, including large domestic animals. The research question of this systematic review was as follows: is facial expression scoring (intervention) a valid method to evaluate pain (the outcome) in large domestic animals (population)?MethodWe searched two databases for relevant articles using the search string: “grimace scale” OR “facial expression” AND animal OR “farm animal” NOT “mouse” NOT “rat” NOT “laboratory animal.” The risk of bias was estimated by adapting the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist.ResultsThe search strategy extracted 30 articles, with the major share on equids and a considerable number on cows, pigs, and sheep. Most studies evaluated facial action units (FAUs), including the eye region, the orbital region, the cheek or the chewing muscles, the lips, the mouth, and the position of the ears. Interobserver reliability was tested in 21 studies. Overall FAU reliability was substantial, but there were differences for individual FAUs. The position of the ear had almost perfect interobserver reliability (interclass coefficient (ICC): 0.73–0.97). Validity was tested in five studies with the reported accuracy values ranging from 68.2 to 80.0%.DiscussionThis systematic review revealed that facial expression scores provide an easy method for learning and reliable test results to identify whether an animal is in pain or distress. Many studies lack a reference standard and a true control group. Further research is warranted to evaluate the test accuracy of facial expression scoring as a live pen side test.

Currently, an effective repair method that can promote satisfactory cartilage regeneration is unavailable for cartilage damages owing to inevitable inflammatory erosion. Cartilage tissue engineering has revealed considerable treatment options for cartilage damages. Icariin (ICA) is a flavonoid component of Epimedii folium with both chondrogenic and anti-inflammatory properties. In this study, we prepared an ICA/CTS hydrogel by loading ICA into chitosan (CTS) hydrogel to impart chondrogenesis and anti-inflammatory properties to the ICA/CTS hydrogel. In vitro results revealed that ICA showed sustained release kinetics from the ICA/CTS hydrogel. In addition, compared to the CTS hydrogel, the ICA/CTS hydrogel exhibited a favorable in vitro anti-inflammatory effect upon incubation with lipopolysaccharide pre-induced RAW264.7 macrophages, as indicated by the suppression of inflammatory-related cytokines (IL-6 and TNF-α). Additionally, when co-cultured with chondrocytes in vitro, the ICA/CTS hydrogel showed good cytocompatibility, accelerated chondrocyte proliferation, and enhanced chondrogenesis compared to the CTS hydrogel. Moreover, the in vitro engineered cartilage from the chondrocyte-loaded ICA/CTS hydrogel achieved stable cartilage regeneration when subcutaneously implanted in a goat model. Finally, the addition of ICA endowed the ICA/CTS hydrogel with a potent anti-inflammatory effect compared to what was observed in the CTS hydrogel, as confirmed by the attenuated IL-1β, IL-6, TNF-α, and TUNEL expression. The prepared ICA/CTS hydrogel offered an effective method of delivery for chondrogenic and anti-inflammatory agents and served as a useful platform for cartilage regeneration in an immunocompetent large animal model.

In recent decades, the pig has attracted considerable attention as an important intermediary model animal in translational biobehavioral research due to major similarities between pig and human neuroanatomy, physiology, and behavior. As a result, there is growing interest in using pigs to model many human neurological conditions and injuries. Pigs are highly intelligent and are capable of performing a wide range of behaviors, which can provide valuable insight into the effects of various neurological disease states. One area in which the pig has emerged as a particularly relevant model species is in the realm of neurotrauma research. Indeed, the number of investigators developing injury models and assessing treatment options in pigs is ever-expanding. In this review, we examine the use of pigs for cognitive and behavioral research as well as some commonly used physiological assessment methods. We also discuss the current usage of pigs as a model for the study of traumatic brain injury. We conclude that the pig is a valuable animal species for studying cognition and the physiological effect of disease, and it has the potential to contribute to the development of new treatments and therapies for human neurological and psychiatric disorders.

Simple Summary: Functional gametes, such as oocytes and spermatozoa, have been derived from rodent pluripotent stem cells, which can be applied to large animals and ultimately, to humans. In addition to summarizing these topics, we also review additional approaches for in vitro reconstitution of reproductive organs. This review illustrates intensive past efforts and future challenges on stem cell research for in vitro biogenesis in various mammalian models. Recent success in derivation of functional gametes (oocytes and spermatozoa) from pluripotent stem cells (PSCs) of rodents has made it feasible for future application to large animals including endangered species and to ultimately humans. Here, we summarize backgrounds and recent studies on in vitro gametogenesis from rodent PSCs, and similar approaches using PSCs from large animals, including livestock, nonhuman primates (NHPs), and humans. We also describe additional developing approaches for in vitro reconstitution of reproductive organs, such as the ovary (ovarioid), testis (testisoid), and future challenges in the uterus (uteroid) and oviduct (oviductoid), all of which may be derived from PSCs. Once established, these in vitro systems may serve as a robust platform for elucidating the pathology of infertility-related disorders and ectopic pregnancy, principle of reproduction, and artificial biogenesis. Therefore, these possibilities, especially when using human cells, require consideration of ethical issues, and international agreements and guidelines need to be raised before opening "Pandora's Box". [ABSTRACT FROM AUTHOR]

There is an unmet need for novel and efficacious therapeutics for regenerating injured articular cartilage in progressive osteoarthritis (OA) and/or trauma. Mesenchymal stem cells (MSCs) are particularly promising for their chondrogenic differentiation, local healing environment modulation, and tissue- and organism-specific activity; however, despite early in vivo success, MSCs require further investigation in highly-translatable models prior to disseminated clinical usage. Large animal models, such as canine, porcine, ruminant, and equine models, are particularly valuable for studying allogenic and xenogenic human MSCs in a human-like osteochondral microenvironment, and thus play a critical role in identifying promising approaches for subsequent clinical investigation. In this mini-review, we focus on [1] considerations for MSC-harnessing studies in each large animal model, [2] source tissues and organisms of MSCs for large animal studies, and [3] tissue engineering strategies for optimizing MSC-based cartilage regeneration in large animal models, with a focus on research published within the last 5 years. We also highlight the dearth of standard assessments and protocols regarding several crucial aspects of MSC-harnessing cartilage regeneration in large animal models, and call for further research to maximize the translatability of future MSC findings.

A disappointing number of new therapies for pulmonary hypertension (PH) have been successfully translated to the clinic. Adeno-associated viral (AAV) gene therapy has the potential to treat the underlying pathology of PH, but the challenge remains in efficient and safe delivery. The aims of this study were (1) to test the efficacy of endobronchial aerosolization delivery for AAV1-mediated sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) gene therapy in a PH pig model and (2) to identify the most efficient airway administration modality for in-lung gene therapy in PH. We hypothesized that delivery to the distal bronchi increases lung viral uptake and avoids virus loss in off-target compartments. In part 1 of the study, PH was induced in pigs by surgically banding the pulmonary veins. Two months postsurgery, 1 × 1013 viral genomes (vg) of AAV1.SERCA2a or saline was endobronchially aerosolized using a bronchoscope. Two months after aerosolization, high vg copies (vgc) were detected in the lungs, accompanied by functional and morphometrical amelioration of PH. In part 2 of the study, we directly compared the endobronchial aerosolization gene delivery to the intratracheal aerosolization in PH pigs. Endobronchial delivery demonstrated higher viral expression (6,719 ± 927 vs. 1,444 ± 402 vgc/100 ng DNA, p = 0.0017), suggesting this delivery modality is a promising method for clinical AAV gene therapy for PH. [ABSTRACT FROM AUTHOR]

Abstract Introduction Animal experiments with large living animals are essential for the development of medical devices and the training of surgical procedures. Swine are frequently used in animal experiments due to their similar size and anatomy compared to humans. However, it is well known that swine has less local bleeding than humans. The aim of the study was to verify whether animal models with appropriate local bleeding capability could be established. Methods The activated clotting time (ACT) was measured for eight swine (piglet, 35 kg) under general anesthesia. The flexible endoscope was advanced orally, and the gastric mucosa was intentionally traumatized to bleed by biopsy forceps, and the time until spontaneous hemostasis was obtained (mucosal bleeding time). Then, heparin (50 U/kg) was administered intravenously. After 10 min, the ACT was remeasured, and the gastric mucosa was again damaged to bleed by biopsy forceps. The mucosal bleeding time was remeasured. The above measurements were repeated until the ACT exceeded 200 s. Results The median ACT values (seconds) were 83 (no heparin), 155 (50 U/kg heparin), and 204 (100 U/kg heparin), which were significantly increased. The median mucosal bleeding times (seconds) were 152 (no heparin), 283 (50 U/kg), and 423 (100 U/kg), which were significantly extended. Conclusion A bleeding animal model for surgical and endoscopic training was successfully established by bolus heparin administration.

State of the art mathematical models are currently used to bridge the gap between basic research conducted in the laboratory and preclinical research conducted on large animals, which ultimately paves the way for clinical translation. In this regard, there is a great need for models that can be used alongside experiments for in-depth investigation and validation. One such experimental model is the porcine atrium, which is commonly used to study the mechanisms of onset and control of atrial fibrillation in the context of its surgical management. However, a mathematical model of pig atria is lacking. In this paper, we present the first ionically detailed mathematical model of porcine atrial electrophysiology, at body temperature. The model includes 12 ionic currents, 4 of which were designed based on experimental patch-clamp data directly obtained from literature. The formulations for the other currents are adopted from the human atrial model, and modified for porcine specificity based on our measured restitution data for different action potential characteristics: resting membrane potential, action potential amplitude, maximum upstroke velocity and action potential duration and different levels of membrane voltage repolarization. The intracellular Ca 2+ dynamics follows the Luo-Rudy formulation for guinea pig ventricular cardiomyocytes. The resulting model represents "normal" cells which are formulated as a system of ordinary differential equations. We extend our model to two dimensions to obtain plane wave propagation in tissue with a velocity of 0.58 m/s and a wavelength of 8 cm. The wavelength reduces to 5 cm when the tissue is paced at 200 ms. Using S1-S2 cross-field protocol, we demonstrate in an 11.26 cm square simulation domain, the ability to initiate single spiral waves (rotation period ≃ 180 ms) that remain stable for more than 40 s. The spiral tip exhibits hypermeander. In agreement with previous experimental results using pig atria, our model shows that early repolarization is primarily driven by a calcium-mediated chloride current, I ClCa , which is completely inactivated at high pacing frequencies. This is a condition that occurs only in porcine atria. Furthermore, the model shows spatiotemporal chaos with reduced repolarization. [ABSTRACT FROM AUTHOR]

State of the art mathematical models are currently used to bridge the gap between basic research conducted in the laboratory and preclinical research conducted on large animals, which ultimately paves the way for clinical translation. In this regard, there is a great need for models that can be used alongside experiments for in-depth investigation and validation. One such experimental model is the porcine atrium, which is commonly used to study the mechanisms of onset and control of atrial fibrillation in the context of its surgical management. However, a mathematical model of pig atria is lacking. In this paper, we present the first ionically detailed mathematical model of porcine atrial electrophysiology, at body temperature. The model includes 12 ionic currents, 4 of which were designed based on experimental patch-clamp data directly obtained from literature. The formulations for the other currents are adopted from the human atrial model, and modified for porcine specificity based on our measured restitution data for different action potential characteristics: resting membrane potential, action potential amplitude, maximum upstroke velocity and action potential duration and different levels of membrane voltage repolarization. The intracellular Ca2+ dynamics follows the Luo-Rudy formulation for guinea pig ventricular cardiomyocytes. The resulting model represents “normal” cells which are formulated as a system of ordinary differential equations. We extend our model to two dimensions to obtain plane wave propagation in tissue with a velocity of 0.58 m/s and a wavelength of 8 cm. The wavelength reduces to 5 cm when the tissue is paced at 200 ms. Using S1-S2 cross-field protocol, we demonstrate in an 11.26 cm square simulation domain, the ability to initiate single spiral waves (rotation period ≃ 180 ms) that remain stable for more than 40 s. The spiral tip exhibits hypermeander. In agreement with previous experimental results using pig atria, our model shows that early repolarization is primarily driven by a calcium-mediated chloride current, IClCa, which is completely inactivated at high pacing frequencies. This is a condition that occurs only in porcine atria. Furthermore, the model shows spatiotemporal chaos with reduced repolarization.

Platelet lysate, derived from platelets, are valuable biological products rich in bioactive molecules. Their use promotes tissue healing and modulates inflammation. However, maintaining the stability and bioactivity of platelet lysate is challenging since they degrade rapidly at room temperature. This study focused on the possibility to confer enhanced stability to freeze-dried equine platelet lysate as an alternative to platelet-rich plasma (PRP). Platelet lysate (PL) was derived from PRP and freeze-dried either as such or using various adjuvants. Primary cell cultures of porcine Vascular Wall-Mesenchymal Stem Cells were treated with different PL formulations, and cell viability was assessed using an MTT assay. Overall, the addition of PL significantly improved cell viability as compared to controls without growth factor supplementation or with foetal bovine serum. Notably, the freeze-drying process maintained the effectiveness of the PL for at least a week. Furthermore, the study revealed that varying the horse as the source of PL could yield varying effects on cell viability. Detailed freeze-drying protocols were established, including freezing, primary drying and secondary drying phases, and the type of adjuvant. This study demonstrated the potential of freeze-dried equine PL as a viable alternative to PRP and highlighted the importance of precise freeze-drying protocols and adjuvants for standardization. Equine PL showed promise for medical treatment in horses, offering advantages such as extended shelf life, ease of handling, and reduced transportation costs, with the potential for broadened therapeutic usage., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The scarcity of ideal biocompatible scaffolds makes the regeneration of cartilage in the subcutaneous environment of large animals difficult. We have previously reported the successful regeneration of good-quality cartilage in a nude mouse model using the electrospun gelatin/polycaprolactone (GT/PCL) nanofiber membranes. The GT/PCL ratios were varied to generate different sets of membranes to conduct the experiments. However, it is unknown whether these GT/PCL membranes can support the process of cartilage regeneration in an immunocompetent large animal model. We seeded swine auricular chondrocytes onto different GT/PCL nanofiber membranes (GT:PCL = 30:70, 50:50, and 70:30) under the sandwich cell-seeding mode. Prior to subcutaneously implanting the samples into an autologous host, they were cultured in vitro over a period of 2 weeks. The results revealed that the nanofiber membranes with different GT/PCL ratios could support the process of subcutaneous cartilage regeneration in an autologous swine model. The maximum extent of homogeneity in the cartilage tissues was achieved when the G5P5 (GT: PC = 50: 50) group was used for the regeneration of cartilage. The formed homogeneous cartilage tissues were characterized by the maximum cartilage formation ratio. The extents of the ingrowth of the fibrous tissues realized and the extents of infiltration of inflammatory cells achieved were found to be the minimum in this case. Quantitative analyses were conducted to determine the wet weight, cartilage-specific extracellular matrix content, and Young’s modulus. The results indicated that the optimal extent of cartilage formation was observed in the G5P5 group. These results indicated that the GT/PCL nanofiber membranes could serve as a potential scaffold for supporting subcutaneous cartilage regeneration under clinical settings. An optimum GT/PCL ratio can promote cartilage formation.

This qualitative study (n = 25) was created to better understand the mental health of U.S. swine veterinarians who were involved in the mass depopulation events related to COVID-19. A total of 25 swine veterinarians, participants in a previous larger quantitative study, volunteered to be interviewed about their experiences related to the COVID-19 mass depopulation event. Themes that emerged from these interviews included: (1) the need to be better prepared for crisis events; (2) lack of public understanding; (3) moral distress; (4) empathy for others, especially young veterinarians; (5) sources of support; (6) pride, honor and gratitude; and (7) an overarching theme of emotional distancing and detachment—concerns external to one’s own mental health. Based on our results, we recommend additional training and supportive services for those who might be involved in future depopulation efforts. Additionally, we suggest that the veterinary profession prioritize public education campaigns to help the public better understand the need for depopulation.

Promising biomaterials should be tested in appropriate large animal models that recapitulate human inflammatory and regenerative responses. Previous studies have shown tyrosine‐derived polycarbonates (TyrPC) are versatile biomaterials with a wide range of applications across multiple disciplines. The library of TyrPC has been well studied and consists of thousands of polymer compositions with tunable mechanical characteristics and degradation and resorption rates that are useful for nerve guidance tubes (NGTs). NGTs made of different TyrPCs have been used in segmental nerve defect models in small animals. The current study is an extension of this work and evaluates NGTs made using two different TyrPC compositions in a 1 cm porcine peripheral nerve repair model. We first evaluated a nondegradable TyrPC formulation, demonstrating proof‐of‐concept chronic regenerative efficacy up to 6 months with similar nerve/muscle electrophysiology and morphometry to the autograft repair control. Next, we characterized the acute regenerative response using a degradable TyrPC formulation. After 2 weeks in vivo, TyrPC NGT promoted greater deposition of pro‐regenerative extracellular matrix (ECM) constituents (in particular collagen I, collagen III, collagen IV, laminin, and fibronectin) compared to commercially available collagen‐based NGTs. This corresponded with dense Schwann cell infiltration and axon extension across the lumen. These findings confirmed results reported previously in a mouse model and reveal that TyrPC NGTs were well tolerated in swine and facilitated host axon regeneration and Schwann cell infiltration in the acute phase across segmental defects ‐ likely by eliciting a favorable neurotrophic ECM milieu. This regenerative response ultimately can contribute to functional recovery. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cells (hPSCs) are derived from human embryos (human embryonic stem cells) or reprogrammed from human somatic cells (human induced pluripotent stem cells). They can differentiate into cardiovascular cells, which have great potential as exogenous cell resources for restoring cardiac structure and function in patients with heart disease or heart failure. A variety of protocols have been developed to generate and expand cardiovascular cells derived from hPSCs in vitro. Precisely and spatiotemporally activating or inhibiting various pathways in hPSCs is required to obtain cardiovascular lineages with high differentiation efficiency. In this concise review, we summarize the protocols of differentiating hPSCs into cardiovascular cells, highlight their therapeutic application for treatment of cardiac diseases in large animal models, and discuss the challenges and limitations in the use of cardiac cells generated from hPSCs for a better clinical application of hPSC-based cardiac cell therapy.

Recent success in derivation of functional gametes (oocytes and spermatozoa) from pluripotent stem cells (PSCs) of rodents has made it feasible for future application to large animals including endangered species and to ultimately humans. Here, we summarize backgrounds and recent studies on in vitro gametogenesis from rodent PSCs, and similar approaches using PSCs from large animals, including livestock, nonhuman primates (NHPs), and humans. We also describe additional developing approaches for in vitro reconstitution of reproductive organs, such as the ovary (ovarioid), testis (testisoid), and future challenges in the uterus (uteroid) and oviduct (oviductoid), all of which may be derived from PSCs. Once established, these in vitro systems may serve as a robust platform for elucidating the pathology of infertility-related disorders and ectopic pregnancy, principle of reproduction, and artificial biogenesis. Therefore, these possibilities, especially when using human cells, require consideration of ethical issues, and international agreements and guidelines need to be raised before opening “Pandora’s Box”.

We have created entirely biological tissue-engineered vascular grafts (TEVGs) using sheets of cell-assembled extracellular matrix (CAM) produced by human fibroblasts in vitro. A large animal TEVG would allow long-term pre-clinical studies in a clinically relevant setting (graft size and allogeneic setting). Therefore, canine, porcine, ovine, and human skin fibroblasts were compared for their ability to form CAM sheets. Serum sourcing greatly influenced CAM production in a species-dependent manner. Ovine cells produced the most homogenous and strongest animal CAM sheets but remained ≈3-fold weaker than human sheets despite variations of serum, ascorbate, insulin, or growth factor supplementations. Key differences in cell growth dynamics, tissue development, and tissue architecture and composition were observed between human and ovine. This study demonstrates critical species-to-species differences in fibroblast behavior and how they pose a challenge when attempting to substitute animal cells for human cells during the development of tissue-engineered constructs that require long-term cultures. [ABSTRACT FROM AUTHOR]

Background: Coronary artery dissection (CAD) sometimes accompanies unstable hemodynamics and requires mechanical cardiac support. Meanwhile, mechanical cardiac support may influence coronary hemodynamics in CAD. No study has examined the impact of Impella left ventricular (LV) support on CAD.Materials and Methods: CAD was induced in eight Yorkshire pigs by injuring the left anterior descending artery (LAD) using a 0.018-in. stiff guidewire and/or deep engagement of a blunt-cut coronary guiding catheter. After the creation of CAD, hemodynamic parameters, coronary pressure, and flow as well as coronary angiograms were acquired before and after maximum LV support using the Impella CP.Result: CADs with a large flap were successfully created by deep engagement of a blunt-tip guiding catheter with forceful contrast injection. One animal (#8) exhibited thrombolysis in myocardial infarction (TIMI)-1 flow, while the others (animals #1–#7) showed TIMI-2/3 flow. In TIMI-2/3 animals, maximal Impella support increased mean coronary pressure (108.4 ± 22.5 to 124.7 ± 28.0 mmHg, P < 0.001) with unchanged mean coronary flow velocity (63.50 ± 28.66 to 48.32 ± 13.30 cm/s, P = 0.17) of the LAD distal to the dissection. The LV end-diastolic pressure (20.6 ± 6.6 vs. 12.0 ± 3.4 mmHg, P = 0.032), LV end-diastolic volume (127 ± 32 vs. 97 ± 26 ml, P = 0.015), stroke volume (68 ± 16 vs. 48 ± 14 ml, P = 0.003), stroke work (5,744 ± 1,866 vs. 4,424 ± 1,650 mmHg·ml, P = 0.003), and heart rate (71.4 ± 6.6 vs. 64.9 ± 9.3/min, P = 0.014) were all significantly reduced by Impella support, indicating effective unloading of the LV. In the TIMI-1 animal (animal #8), maximal Impella support resulted in further delay in angiographic coronary flow and reduced distal coronary pressure (22.9–17.1 mmHg), together with increased false-lumen pressure.Conclusion: Impella support effectively unloaded the LV and maintained the hemodynamics in a novel porcine model of CAD. Coronary pressure distal to the dissection was increased in TIMI-2/3 animals after Impella support but decreased in the animal with initial TIMI-1 flow.

Large animal teaching hospitals often struggle to maintain consistent teaching caseloads, which are affected by seasonal variations, economic pressures, increased abilities of local large animal practices to hospitalize large animals, and client intolerance for the operational needs of an academic mission. Non-academic large animal practices enjoy a more consistent caseload but suffer from a lack of emergency relief and a limited ability to share emergency duties, which may have adverse effects on work-life balance. An academic, on-farm, large animal emergency relief service can combine multiple clinics' emergency services to increase overall caseload and the probability of consistent teaching exposure for veterinary students. In late November of 2013, the Large Animal Teaching Hospital at the University of Tennessee, College of Veterinary Medicine adopted a business model to provide a large animal emergency relief service to area practitioners; enhance student learning via increased emergency caseload; and advance the academic mission to develop practice-ready graduates. Providing this service contributes to the well-being of area practitioners and enriches student learning through increased caseload.

Traumatic brain injury (TBI) is a leading cause of morbidity worldwide, with patients often suffering from consequences such as cognitive deficits, social abnormalities, anxiety, depression, pain, and motor dysfunction. Given that these impairments often have a significant impact on the patient's quality of life, a key aim of therapeutic intervention in TBI is to mitigate these effects. Translational strategies to develop such interventions have heavily featured animal models of TBI. To assess the efficacy of interventions in these models, a range of behavioral outcomes are utilized. However, in light of the past translational failures that have plagued the TBI field, the clinical relevance of these preclinical behavioral tests is now being scrutinized. This article will summarize the behavioral consequences of TBI in humans; describe common methods available for testing cognition, social function, motor ability, pain, as well as depression- and anxiety-like behaviors in animal models of TBI; provide an overview of the results from TBI animal model studies that have utilized these methods; and discuss these pre-clinical behavior methods and findings in terms of their relevance to the clinical TBI setting. We conclude that there is translational value in these methods and their related findings, but also suggest strategies and future research to improve the clinical relevance of behavior testing in animal models of TBI. [ABSTRACT FROM AUTHOR]

An important factor for successful translational stroke research is study quality. Low-quality studies are at risk of biased results and effect overestimation, as has been intensely discussed for small animal stroke research. However, little is known about the methodological rigor and quality in large animal stroke models, which are becoming more frequently used in the field. Based on research in two databases, this systematic review surveys and analyses the methodological quality in large animal stroke research. Quality analysis was based on the Stroke Therapy Academic Industry Roundtable and the Animals in Research: Reporting In Vivo Experiments guidelines. Our analysis revealed that large animal models are utilized with similar shortcomings as small animal models. Moreover, translational benefits of large animal models may be limited due to lacking implementation of important quality criteria such as randomization, allocation concealment, and blinded assessment of outcome. On the other hand, an increase of study quality over time and a positive correlation between study quality and journal impact factor were identified. Based on the obtained findings, we derive recommendations for optimal study planning, conducting, and data analysis/reporting when using large animal stroke models to fully benefit from the translational advantages offered by these models. [ABSTRACT FROM AUTHOR]

Background Context: The interface and interactions between an interbody cage, graft material, and host bone can all participate in the fusion. Shortcomings of Poly(aryl-ether-ether-ketone) interbody cages have been addressed with novel titanium surfaces. Titanium surfaces paired with macroscale topography features on the endplates and within the aperture may provide additional benefits.Purpose: To evaluate the influence of cage design parameters on interbody fusion in a large animal preclinical model.Study Design/setting: A comparative preclinical large animal model was performed to evaluate how macroscale topography features of an interbody cage can facilitate early integration between the host bone, graft material, and interbody cage and these effects on biomechanical stability and fusion.Methods: Forty single level interbody fusions (L4-L5) using iliac crest autograft and bilateral pedicle screw fixation were performed in adult sheep to evaluate the effect of undercut macrostructure topography features of an interbody cage on the endplates and within the aperture. Fusions were evaluated at 6 and 12 weeks (n=10 per group) using radiography, microcomputed tomography, biomechanical integrity, and histology endpoints.Results: The presence of the undercut macrostructures present on the endplates and within the aperture statistically improved biomechanical integrity at 6 and 12 weeks compared with controls. Microcomputed tomography and histology demonstrated bony interdigitation within the endplate and aperture features contributing to the improvement in properties.Conclusions: The present study demonstrates that Poly(aryl-ether-ether-ketone) implants with titanium surfaces can be augmented by undercut macrostructures present on the endplates and within the aperture to provide opportunities for a series of anchoring points that, with new bone formation and remodelling, result in earlier and improved biomechanical integrity of the treated level.Clinical Significance: This preclinical study showed that bone interdigitation with the undercut macrostructures present on the endplates and within the aperture resulted in improved fusion and biomechanical stability in a clinically relevant spinal fusion model. Future clinical study is warranted to evaluate such implants' performance in humans. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of changes in intraabdominal pressure (IAP) on central venous pressure (CVP) in normal horses. Design: Experimental, in vivo study. Setting: University Teaching Hospital. Animals: Convenience sample of 7 mixed breed horses—5 geldings and 2 mares. Interventions: Pneumoperitoneum was induced in horses under standing sedation with carbon dioxide gas using a laparoscopic insufflator for a total of 60 minutes to simulate clinical elevation in IAP. Pressure was increased stepwise to 20 mm Hg over 30 minutes, and maintained at that pressure for 30 minutes to evaluate the effect of sustained intraabdominal hypertension. CVP was obtained from the cranial vena cava, concurrent with pressure obtained from the peritoneal cavity. Measurements and main results: CVP increased as IAP increased up to 12 mm Hg, and declined as IAP increased further. The changes in CVP over time were significantly different (P < 0.03). Repeated measures correlation was positive, and highest, for mean CVP as IAP increased from 0 to 12 mm Hg (r =.70; 95% CI,.43–.85; P < 0.0001). Correlation of mean CVP with insufflation pressure became negative as IAP increased further from 15 to 20 mm Hg (r = –.47; 95% CI, –.66 to –.21; P = 0.0006). Conclusions: This report provides preliminary data demonstrating a biphasic trend in equine CVP caused by changes in IAP, similar to that observed in other species. Further investigations are needed to evaluate this trend and to confirm these results in clinical patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of changes in intra‐abdominal pressure (IAP) on medial saphenous venous pressure (MSVP) and hemodynamics in normal horses. Design: Experimental, in‐vivo study. Setting: University Teaching Hospital. Animals: Convenience sample of 7 mixed breed horses; 5 geldings, and 2 mares. Interventions: Pneumoperitoneum was induced in horses under standing sedation with carbon dioxide gas using a laparoscopic insufflator for a total of 60 minutes to simulate clinical elevation in IAP. Pressure was increased stepwise to 20 mm Hg over 30 minutes, and maintained at that pressure for 30 minutes to evaluate the effect of sustained intra‐abdominal hypertension. The MSVP and vital parameters were recorded, along with direct arterial blood pressure from the transverse facial artery. Measurements and Main Results: As IAP increased, MSVP increased in a stepwise manner, in concert with changes in IAP. The consistency in measurement between MSVP and IAP was high (intraclass correlation coefficient = 0.92; P < 0.001) and repeated measures correlation was excellent (r = 0.98; P < 0.001). Heart rate was unchanged over the course of the experiment (P = 0.09), however, respiratory rate increased with increasing IAP (P < 0.001). Arterial blood pressure also increased with insufflation (P < 0.001), with a significant difference at an IAP of 15 mm Hg (P = 0.04). Conclusions: This report provides preliminary data demonstrating a strong correlation between equine MSVP and changes in IAP, similar to that observed in other species. Further investigations are needed to evaluate this relationship, and to confirm these results in clinical patients. [ABSTRACT FROM AUTHOR]

Large animal models have been widely used to facilitate the translation of mesenchymal stem cells (MSC) from the laboratory to patient. MSC, with their multi-potent capacity, have been proposed to have therapeutic benefits in a number of pathological conditions. Laboratory studies allow the investigation of cellular and molecular interactions, while small animal models allow initial 'proof of concept' experiments. Large animals (dogs, pigs, sheep, goats and horses) are more similar physiologically and structurally to man. These models have allowed clinically relevant assessments of safety, efficacy and dosing of different MSC sources prior to clinical trials. In this review, we recapitulate the use of large animal models to facilitate the use of MSC to treat myocardial infarction—an example of one large animal model being considered the 'gold standard' for research and osteoarthritis—an example of the complexities of using different large animal models in a multifactorial disease. These examples show how large animals can provide a research platform that can be used to evaluate the value of cell-based therapies and facilitate the process of 'bench to bedside'. [ABSTRACT FROM AUTHOR]