Differential Effects of Various Cytokine Priming on T Cell Suppression and Migration in Canine Mesenchymal Stem Cells.

Mesenchymal stem cells have been widely studied for treating immune-mediated diseases due to their immunomodulatory abilities. Recent studies have shown that priming MSCs with inflammatory cytokines can enhance these functions, yet the optimal priming conditions for canine MSCs remain poorly defined. In this study, we investigated the effects of priming canine adipose tissue-derived MSCs (cAMSCs) with inflammatory cytokines IFN-γ, TNF-α, and IL-17 at various concentrations (10, 20, and 50 ng/mL) to evaluate their immunomodulatory and migratory capacities.

Immunomodulatory, anti-synoviocyte, and anti-osteoclastic abilities of embryonic stem cell-derived mesenchymal stem cells in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, fibroblast-like synoviocyte hyperactivation, and osteoclast-mediated bone destruction. Mesenchymal stem cells (MSCs) derived from adult tissues exhibit therapeutic potential owing to their regenerative and immunomodulatory properties; However, commercialization remains challenging due to limitations in large-scale production with consistent quality. Contrastingly, MSCs derived from embryonic stem cells can be continuously produced and exhibit minimal variation, with high biological and genetic uniformity.

Variations in skin biophysical parameters with age, sex and breed in dogs.

Background: Understanding the physiological and biophysical characteristics of skin provides information for developing appropriate management strategies for skin diseases. However, in dogs, variations in skin biophysical parameters, such as age, sex and breed, remain poorly understood.

Hypothesis/objectives: This study analysed three biophysical characteristics of healthy dog skin (hydration, pH and sebum content) and investigated the effects of sex, age and breed.

Treatment of Premature Ovarian Failure Mouse Model Using Granulosa-Like Cells Derived from Wharton's Jelly-Mesenchymal Stem Cells.

Premature ovarian failure (POF) is a significant reproductive disorder characterized by the loss of ovarian function, leading to infertility and endocrine disruption. Hormone replacement therapy (HRT) remains the most commonly used clinical treatment for POF. However, in patients with a history of ovarian or breast cancer, HRT poses significant risks, necessitating the development of alternative approaches.

Gender difference of Wharton's jelly-derived mesenchymal stem cells on differentiation potential into functional granulosa cells.

The ovarian follicles consist of theca and granulosa cells, which play a crucial physiological role in sex hormone and cytokine secretion and provide an optimal induction microenvironment for oocytes. However, ethical concerns and the absence of a cellular model for investigating the molecular pathway in humans present challenges for research on granulosa cells. To address these challenges, differentiation induction into granulosa cells using mesenchymal stem cells (MSCs) could offer a novel approach to advancing granulosa cell research.

Trichostatin A-Induced Epigenetic Modifications and Their Influence on the Development of Porcine Cloned Embryos Derived from Bone Marrow-Mesenchymal Stem Cells.

Abnormal epigenetic reprogramming of nuclear-transferred (NT) embryos leads to the limited efficiency of producing cloned animals. Trichostatin A (TSA), a histone deacetylase inhibitor, improves NT embryo development, but its role in histone acetylation in porcine embryos cloned with mesenchymal stem cells (MSCs) is not fully understood. This study aimed to compare the effects of TSA on embryo development, histone acetylation patterns, and key epigenetic-related genes between in vitro fertilization (IVF), NT-MSC, and 40 nM TSA-treated NT-MSC (T-NT-MSC).

Porcine myogenesis in cloned wildtype and MYF5/MYOD/MYF6-null porcine embryo.

The pig is an important animal model increasingly used for biomedical research, particularly in transplantation strategies involving xenotransplantation or the development of human organs in pig for exotransplantation. Pigs, however, are less characterized than other animal models. In this study, we produced wildtype (WT) pig embryos via somatic cell nuclear transfer (SCNT) technology and compared them to skeletal muscle null embryos (lacking MYF5/MYOD/MYF6) at embryonic day 41, 62, and 90, critical stages of porcine myogenesis.

Increased apoptosis in late-developing in vitro fertilized bovine blastocysts decreases successful pregnancy.

Objective: Pregnancy in cattle after embryo transfer (ET) is influenced by several factors, including embryo quality. Therefore, preparing high-quality embryos with the greatest developmental potential is essential for achieving a successful pregnancy after ET. Meanwhile, blastocysts produced by in vitro fertilization (IVF) procedure have different developmental speed during in vitro culture (IVC) and they exhibited different competence in the establishment of pregnancy.

Circulatory age-associated B cells: Their distinct transcriptomic characteristics and clinical significance in drug-naïve patients with rheumatoid arthritis.

Age-associated B cells (ABCs) have been implicated in the pathogenesis of autoimmune diseases. However, the global gene expression and clinical significance of circulatory ABCs in rheumatoid arthritis (RA) remain poorly understood. Here, single-cell RNA sequencing identified nine B cell subsets in peripheral blood of RA patients, including ABCs.

Regulation of Colonic Inflammation and Macrophage Homeostasis of IFN-γ-Primed Canine AMSCs in Experimental Colitis in Mice.

Mesenchymal stem cells (MSCs) have shown potential in treating immune-mediated diseases due to their immunomodulatory properties, which can be enhanced by priming with inflammatory cytokines like interferon-gamma (IFN-γ). This study evaluates the therapeutic effects of IFN-γ-primed canine adipose tissue-derived MSCs (AMSCs) in a mouse model of inflammatory bowel disease (IBD). Canine AMSCs were primed with 50 ng/mL recombinant canine IFN-γ for 48 h, and the effects were compared to those seen in naïve (unprimed) AMSCs.

Identification of Reference Gene for Quantitative Gene Expression in Early-Term and Late-Term Cultured Canine Fibroblasts Derived from Ear Skin.

Fibroblasts are cells that reside within the fibrous or loose connective tissues of most mammalian organs. For research purposes, fibroblasts are often subjected to long-term culture under defined conditions, during which their properties can significantly change. It is essential to understand and document these changes to obtain reliable outcomes.

Genome-Wide Characterization of Somatic Mutation Patterns in Cloned Dogs Reveals Implications for Neuronal Function, Tumorigenesis, and Aging.

Studies on somatic mutations in cloned animals have revealed slight genetic variances between clones and their originals, but have yet to identify the precise effects of these differences within the organism. Somatic mutations contribute to aging and are implicated in tumor development and other age-related diseases. Thus, we compared whole genome sequencing data from an original dog with that of cloned dogs, identifying candidate somatic mutations that were disproportionately located within genes previously implicated in aging.

The autoimmune response induced by α-synuclein peptides drives neuronal cell death and glial cell activation.

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses.

RNA sequencing provides novel insights into the pathogenesis of naturally occurring myxomatous mitral valve disease stage B1 in beagle dogs.

Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disorder in dogs with a high prevalence, accounting for approximately 75% of all canine heart disease cases. MMVD is a complex disease and shows variable progression from mild valve leakage to severe regurgitation, potentially leading to heart failure. However, the molecular mechanisms and age-related changes that govern disease progression, especially at the early stage (B1) before the development of discernable clinical signs, remain poorly understood.

Insensitive Effects of Inflammatory Cytokines on the Reference Genes of Synovial Fluid Resident-Mesenchymal Stem Cells Derived from Rheumatoid Arthritis Patients.

Mesenchymal stem cells derived from rheumatoid arthritis patients (RA-MSCs) provide an understanding of a variety of cellular and immunological responses within the inflammatory milieu. Sustained exposure of MSCs to inflammatory cytokines is likely to exert an influence on genetic variations, including reference genes (RGs). The sensitive effect of cytokines on the reference genes of RA-SF-MSCs may be a variation factor affecting patient-derived MSCs as well as the accuracy and reliability of data.

Blastocyst complementation and interspecies chimeras in gene edited pigs.

The only curative therapy for many endstage diseases is allograft organ transplantation. Due to the limited supply of donor organs, relatively few patients are recipients of a transplanted organ. Therefore, new strategies are warranted to address this unmet need.

PPIA, HPRT1, and YWHAZ are suitable reference genes for quantitative polymerase chain reaction assay of the hypothalamic-pituitary-gonadal axis in sows.

Objective: The quantitative reverse transcription polymerase chain reaction (qPCR) is the most accurate and reliable technique for analysis of gene expression. Endogenous reference genes (RGs) have been used to normalize qPCR data, although their expression may vary in different tissues and experimental conditions. Verification of the stability of RGs in selected samples is a prerequisite for reliable results.

Lymph node fibroblastic reticular cells regulate differentiation and function of CD4 T cells via CD25.

Lymph node fibroblastic reticular cells (LN-FRCs) provide functional structure to LNs and play important roles in interactions between T cells and antigen-presenting cells. However, the direct impact of LN-FRCs on naive CD4+ T cell differentiation has not been explored. Here, we show that T cell zone FRCs of LNs (LN-TRCs) express CD25, the α chain of the IL-2 receptor heterotrimer.

Lessons From the Success and Failure of Targeted Drugs for Rheumatoid Arthritis: Perspectives for Effective Basic and Translational Research.

Rheumatoid arthritis (RA) is a representative autoimmune disease that is primarily characterized by persistent inflammation and progressive destruction of synovial joints. RA has a complex and heterogeneous pathophysiology, involving interactions among various immune and joint stromal cells and a diverse network of cytokines and intracellular signaling pathways. With improved understanding of RA, over the past decades, therapeutic strategies have become considerably advanced and now included targeted molecular therapies, such as tumor necrosis factor inhibitors, IL-6 blockers, B-cell depletion agents, as well as inhibitors of T-cell co-stimulation and Janus kinases.

Brachygnathia Inferior in Cloned Dogs Is Possibly Correlated with Variants of Wnt Signaling Pathway Initiators.

Abnormalities in animals cloned via somatic cell nuclear transfer (SCNT) have been reported. In this study, to produce bomb-sniffing dogs, we successfully cloned four healthy dogs through SCNT using the same donor genome from the skin of a male German shepherd old dog. Veterinary diagnosis (X-ray/3D-CT imaging) revealed that two cloned dogs showed normal phenotypes, whereas the others showed abnormal shortening of the mandible (brachygnathia inferior) at 1 month after birth, even though they were cloned under the same conditions except for the oocyte source.

Dental pulp-derived stem cells can counterbalance peripheral nerve injury-induced oxidative stress and supraspinal neuro-inflammation in rat brain.

Previously, we reported the successful regeneration of injured peripheral nerves using human dental pulp stem cells (DPSCs) or differentiated neuronal cells from DPSCs (DF-DPSCs) in a rat model. Here, we attempted to evaluate oxidative stress and supraspinal neuro-inflammation in rat brain after sciatic nerve injury (SNI). We divided our experimental animals into three SNI groups based on time.

Pancreatic endocrine-like cells differentiated from human umbilical cords Wharton's jelly mesenchymal stem cells using small molecules.

Following success of pancreatic islet transplantation in the treatment of Type I diabetes mellitus, there is a growing interest in using cell-based treatment approaches. However, severe shortage of donor islets-pancreas impeded the growth, and made researchers to search for an alternative treatment approaches. In this context, recently, stem cell-based therapy has gained more attention.