Selected Grantee Publications
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- 61 results found
- Other Animal Models
- Swine Models
MARCKS Protein Is a Potential Target in a Naturally Occurring Equine Model of Neutrophilic Asthma
Conley et al., Respiratory Research. 2025.
https://pubmed.ncbi.nlm.nih.gov/40176021
Asthma is a chronic inflammatory airway disease that affects millions of people worldwide. Horses spontaneously develop asthma similar to humans, making the equine model ideal for studying airway inflammation. This study revealed that Myristoylated Alanine Rich C Kinase Substrate (MARCKS) protein levels were elevated in immune cells (macrophages and neutrophils) of male and female horses. Blocking this protein reduced inflammatory responses in these cells, suggesting that MARCKS may play a key role in driving asthma symptoms. These findings suggest that the MARCKS protein could potentially be a therapeutic target to reduce inflammation in severe neutrophilic asthma cases. Supported by ORIP (T32OD011130).
Effect of Omeprazole on Esophageal Microbiota in Dogs Detected Using a Minimally Invasive Sampling Method
Handa et al., Journal of Veterinary Internal Medicine. 2025.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11864821
Omeprazole alters the esophageal microbiome (EM) of humans and has associated effects. The changes and subsequent recovery of the EM in 3- to 6-year-old dogs after omeprazole treatment were assessed using the esophageal string test (EST). All 10 dogs tolerated the EST without adverse effects, and the EST retrieved sufficient biofluid to characterize the EM. Diversity analysis revealed no significant alterations in alpha (Observed species, Shannon and Simpson indices) and beta diversity (Bray‐Curtis) across the time points after omeprazole administration. Thus, omeprazole therapy was not observed to alter the EM of healthy dogs in this study. The application of EST in dogs illustrates its use as a minimally invasive tool for investigating the role of EM in esophageal health and disease in dogs. Supported by ORIP (K01OD030515).
Early Results of an Infant Model of Orthotopic Cardiac Xenotransplantation
Mitchell et al., Journal of Heart and Lung Transplantation. 2025.
https://pubmed.ncbi.nlm.nih.gov/39778609
This study evaluated the potential of genetically engineered pig hearts for human pediatric heart failure patients, with 11 infantile pig heart transplants performed in size-matched infant baboons (Papio anubis) (sex not specified). All grafts supported normal cardiac functions post-operatively, and six animals survived beyond 3 months. While early cardiac function was not a limiting factor for survival, systemic inflammation led to pulmonary edema and pleural effusions, which impeded long-term outcomes. These findings highlight the feasibility of cardiac xenotransplantation in infants and underscore the need for targeted therapies to manage inflammation and improve survival. Supported by ORIP (P40OD024628) and NHLBI.
Local Tissue Response to a C-X-C Motif Chemokine Ligand 12 Therapy for Fecal Incontinence in a Rabbit Model
Ruetten et al., American Journal of Physiology—Gastrointestinal and Liver Physiology. 2025.
https://pubmed.ncbi.nlm.nih.gov/39745592
Obstetric anal sphincter injury (OASI) occurs in 2–7% of vaginal childbirths. Surgical interventions for OASI are suboptimal, with 30% of women reporting continued reduction in quality of life due to long-term fecal incontinence. Researchers used a 4- to 5-month-old female New Zealand white rabbit model for OASI to determine whether local C-X-C motif chemokine ligand 12 (CXCL12) injection reduces postinjury pathologies. Treatment with CXCL12 significantly reduced fibrosis. Untreated rabbits demonstrated reduced distinction of anal sphincter skeletal muscle layering and significantly increased the amount of fibrosis. Treatment with CXCL12 did not affect recruitment of CD34+ cells, the number of PAX7+ satellite cells, or innervation and vascularization of skeletal muscle. This pilot study demonstrates the potential of a novel therapeutic for OASI. Supported by ORIP (T32OD010957).
Peripherally Mediated Opioid Combination Therapy in Mouse and Pig
Peterson et al., The Journal of Pain. 2025.
https://pubmed.ncbi.nlm.nih.gov/39542192
This study evaluates novel opioid combinations for pain relief with reduced side effects. Researchers investigated loperamide (a μ-opioid agonist) with either oxymorphindole or N‑benzyl-oxymorphindole—both δ-opioid receptor partial agonists—in mice (male and female) and pigs (male). These combinations produced synergistic analgesia across species without causing adverse effects or respiratory depression. The therapies significantly reduced hypersensitivity in post-injury models, outperforming morphine alone. These findings suggest that peripherally acting opioid combinations can offer effective, safer alternatives for pain management, potentially lowering opioid misuse and side effects. This approach could improve clinical strategies for treating chronic and acute pain with limited central opioid exposure. Supported by ORIP (T32OD010993), NHLBI, and NIDA.
Spatiotemporal Characterization of Cyclooxygenase Pathway Enzymes During Vertebrate Embryonic Development
Leathers et al., Developmental Biology. 2025.
https://pubmed.ncbi.nlm.nih.gov/39581452/
The cyclooxygenase (COX) pathway plays a fundamental role in embryonic development. Disruptions of the COX pathway during pregnancy cause developmental anomalies, including craniofacial clefts, impaired gut innervation, and neural tube defects in the embryo. Researchers used Gallus gallus embryos to study the expression of COX pathway enzymes during neurulation. COX-1 protein expression was upregulated in cells undergoing mitosis, whereas COX-2 protein expression was ubiquitous. This study provides spatiotemporal expression data of COX pathway enzymes at key embryonic development stages in G. gallus and guides future studies focused on defining the role of these enzymes during embryonic development. Supported by ORIP (T35OD010956), NEI, NIDCR, and NIGMS.
Single-Cell Transcriptomics Predict Novel Potential Regulators of Acute Epithelial Restitution in the Ischemia-Injured Intestine
Rose et al., American Journal of Physiology-Gastrointestinal and Liver Physiology. 2025.
https://pubmed.ncbi.nlm.nih.gov/39853303
Following ischemia in the small intestine, early barrier restoration relies on epithelial restitution to reseal the physical barrier and prevent sepsis. Pigs share a similar gastrointestinal anatomy, physiology, and microbiota with humans. Researchers used neonatal and juvenile, 2- to 6-week-old male and female Yorkshire cross pigs to determine upstream regulators of restitution. Single-cell sequencing of ischemia-injured epithelial cells demonstrated two sub-phenotypes of absorptive enterocytes, with one subset presenting a restitution phenotype. Colony-stimulating factor-1 (CSF1) was the only predicted upstream regulator expressed in juvenile jejunum compared with neonatal jejunum. An in vitro scratch wound assay using IPEC-J2 cells showed that BLZ945, a colony-stimulating factor 1 receptor antagonist, inhibited restitution. Ex vivo ischemia-injured neonatal pig jejunum treated with exogenous CSF1 displayed increased barrier function. This study could inform future research focused on developing novel therapeutics for intestinal barrier injury in patients. Supported by ORIP (T32OD011130, K01OD028207), NCATS, NICHD, and NIDDK.
Matrikine Stimulation of Equine Synovial Fibroblasts and Chondrocytes Results in an In Vitro Osteoarthritis Phenotype
Gagliardi et al., Journal of Orthopaedic Research. 2025.
https://pubmed.ncbi.nlm.nih.gov/39486895
Advancements in therapy development for osteoarthritis (OA) currently are limited due to a lack of physiologically relevant in vitro models. This study aimed to understand the effect of matrikine stimulation, using human recombinant fibronectin fragment containing domains 7–10 (FN7–10), on equine synovial fibroblasts and chondrocytes. Inflammatory cytokines, chemokines, and matrix degradation genes in equine synovial fibroblasts and chondrocytes were significantly altered in response to FN7–10 stimulation; marked upregulation was observed in interleukin-6 (IL-6), IL-4, IL-10, matrix metalloproteinase 1 (MMP1), MMP3, MMP13, CCL2/MCP1, and CXCL6/GCP-2 gene expression. Only IL-6 protein production was significantly increased in media isolated from cells stimulated with FN7–10. These results support the potential use of equine synovial fibroblasts and chondrocytes—employing FN7–10—as representative in vitro models to study OA. Supported by ORIP (T32OD011130) and NIAMS.
Biocompatibility and Bone Regeneration by Shape Memory Polymer Scaffolds
Gasson et al., Journal of Biomedical Materials Research Part A. 2025.
https://pubmed.ncbi.nlm.nih.gov/39404147
This study evaluates the potential of shape memory polymer (SMP) scaffolds for bone tissue engineering, focusing on their biocompatibility and ability to support bone regeneration. Researchers first demonstrated biocompatibility of SMP scaffolds in 12-week-old male Wistar rats and confirmed cell adhesion, proliferation, and differentiation, while promoting bone regeneration in 6 month-old male New Zealand white rabbits with induced bone defects. These scaffolds combine mechanical strength with the capacity to enhance biological healing, making them a promising tool for orthopedic applications. These findings highlight the potential of SMPs as a versatile platform for tissue engineering applications, combining structural support with biocompatibility to enhance bone repair and healing outcomes. Supported by ORIP (T32OD011083).
Response of Spontaneous Oral Tumors in Canine Cancer Patients Treated With Stereotactic Body Radiation Therapy (SBRT)
Gualtieri et al., Radiation Research. 2024.
https://pubmed.ncbi.nlm.nih.gov/39478420
This single-institution retrospective study assessed outcomes in 98 dogs with oral tumors after treatment with SBRT. Overall, progression-free survival (PFS) was 152 days, and median survival time (MST) was 270 days for dogs with oral malignant melanoma, squamous cell carcinoma, and soft tissue sarcoma following SBRT, with no significant differences among the groups. Shortened PFS and MST were associated with lymph node metastasis and the use of elective nodal irradiation. Adverse effects of SBRT were common within the study population and included organ toxicities (11.8%) and the formation of certain fistulas (28.4%). The authors concluded that the presence of these adverse effects warrants a re-evaluation of SBRT risk factors and protocols. Supported by ORIP (K01OD031809).