Effect of Allogeneic Oral Mucosa Mesenchymal Stromal Cells on Equine Wound Repair.

OBJECTIVE: To assess the clinical value and safety of the application of allogeneic equine oral mucosa mesenchymal stromal cells (OM-MSCs) to wounds. Animals. 8 healthy adult horses without front limb skin lesions or musculoskeletal disease. Procedures. Stem cells were isolated from the oral mucosa of a donor horse. Horses were subjected to the creation of eight full-thickness cutaneous wounds, two on each distal forelimb (FL) and two on both sides of the thorax (TH). Each wound was subjected to one out of four treatments: no medication (T1), hyaluronic acid- (HA-) gel containing OM-MSC (T2), HA-gel containing OM-MSC secretome (T3), and HA-gel alone (T4). Gross macroscopic evaluation and laser digital photographic documentation were regularly performed to allow wound assessment including wound surface area. Full-thickness skin punch biopsy was performed at each site before wound induction (D0, normal skin) and after complete wound healing (D62, repaired skin). RESULTS: All wounds healed without adverse effect at D62. Distal limb wounds are slower to heal than body wounds. OM-MSC and its secretome have a positive impact on TH wound contraction. OM-MSC has a positive impact on the contraction and epithelialization of FL wounds. No significant difference between wound sites before and after treatment was noted at histological examination. Conclusion and Clinical Relevance. Using horse cells harvested from oral mucosa is a feasible technique to produce OM-MSC or its secretome. The gel produced by the combination of these biologic components with HA shows a positive impact when applied during the early stage of wound healing.

Scientific and Regulatory Policy Committee Points to Consider*: Approaches to the Conduct and Interpretation of Vaccine Safety Studies for Clinical and Anatomic Pathologists.

The design and execution of toxicology studies supporting vaccine development have some unique considerations relative to those supporting traditional small molecules and biologics. A working group of the Society of Toxicologic Pathology Scientific and Regulatory Policy Committee conducted a review of the scientific, technical, and regulatory considerations for veterinary pathologists and toxicologists related to the design and evaluation of regulatory toxicology studies supporting vaccine clinical trials. Much of the information in this document focuses on the development of prophylactic vaccines for infectious agents. Many of these considerations also apply to therapeutic vaccine development (such as vaccines directed against cancer epitopes); important differences will be identified in various sections as appropriate. The topics addressed in this Points to Consider article include regulatory guidelines for nonclinical vaccine studies, study design (including species selection), technical considerations in dosing and injection site collection, study end point evaluation, and data interpretation. The intent of this publication is to share learnings related to nonclinical studies to support vaccine development to help others as they move into this therapeutic area. [Box: see text].

Pre- and Postnatal Development of the Eye: A Species Comparison.

In this review paper, literature data on pre- and postnatal eye development are compared between humans and nonclinical species that are commonly used for human safety assessment, namely, mouse, rat, rabbit, dog, minipig, and nonhuman primates. Some new data on rat and minipig ocular development are also included. This compiled information can be helpful for species selection in juvenile toxicity studies or assist in the interpretation of (non)clinical data during pediatric drug development. Despite some differences in developmental windows and anatomical peculiarities, such as the lack of a fovea centralis in nonprimate species or the presence of a nictitating membrane in some nonclinical species, the functioning and development of the eye is strikingly similar between humans and other mammals. As such, all commonly used nonclinical species appear to be relatively good models for human eye development, although some practical constraints such as size may be a limiting factor. Birth Defects Research 109:1540-1567, 2017. © 2017 Wiley Periodicals, Inc.

Spontaneous testicular tubular hypoplasia/atrophy in the Göttingen minipig: a retrospective study.

The aim of this retrospective study was to assess the incidence and severity of tubular atrophy/hypoplasia in the testes of 104 control Göttingen minipigs aged 4.5 to 15 months. The finding was termed "tubular hypoplasia/atrophy" according to published descriptions for the dog. It included different microscopic changes that were considered part of a continuum, namely seminiferous epithelium vacuolation, presence of multinucleated germ cells in the tubular lumen, and decreased numbers (hypospermatogenesis) or absence of germ cells. This retrospective study demonstrates that tubular hypoplasia/atrophy is present in more than 70% of Göttingen minipigs and can occur at a marked severity in control animals. It correlated with a higher level of cell debris and a decrease in sperm content in the epididymides and with lower absolute and relative testes weights. There was no correlation with the weight of other sexual organs, total bodyweight, or age, which demonstrates that this change was not related to sexual immaturity. The distinction between this background finding and a compound-related effect could be challenging for the pathologist.

A review of background findings in cynomolgus monkeys (Macaca fascicularis) from three different geographical origins.

This review was performed to assess variations in background observations in cynomolgus macaques (Macaca fascicularis) originating from three breeding centres located in Mauritius, The Philippines and Vietnam. The data and tissue samples from 90 cynomolgus monkeys (approximately evenly distributed between the three sources) comprising the control groups from 11 regulatory toxicology studies were used for this investigation. Clinical data--age, body weight, organ weights, haematology and serum biochemistry--were analyzed. Samples of stomach, colon, kidney, heart, liver, spleen and lung were examined microscopically and graded to characterize the degree of lymphoplasmacytic cell infiltration. The main microscopic origin-related variations concerned the digestive tract, where the lymphoplasmacytic cell infiltration grade was significantly lower (p0.001) in cynomolgus monkeys from Mauritius when compared with those from Asia. Generally, only the antral mucosa of the stomach was infiltrated in cynomolgus monkeys from The Philippines, whereas both the fundic and antral regions were infiltrated in those from Vietnam. The digestive tract infiltration grade was strongly correlated with the mean white blood cell count in monkeys from all three sources. Spiral-shaped bacteria were observed in the stomach of monkeys from all three sources, but their presence did not correlate with the severity of the gastric infiltrate. Helicobacter heilmannii-type bacteria were almost always seen in the fundus, Helicobacter pylori-type bacteria were only occasionally seen in the antral region. The incidences of other microscopic findings, such as urothelial cytoplasmic inclusions or Balantidium coli in the caecum, also varied according to the source of the monkeys. Some variations in relative organ weights, haematology and serum biochemistry were also related to the origin of the monkeys, but these did not correlate with the microscopic findings.

Subcutaneous microchip-associated tumours in B6C3F1 mice: a retrospective study to attempt to determine their histogenesis.

Fifty-two subcutaneous tumours associated with microchip were collected from three carcinogenicity B6C3F1 mice studies. Two of these 52 tumours were adenocarcinoma of the mammary gland located on the dorsal region forming around the chip. All the other 50 were mesenchymal in origin and were difficult to classify on morphological grounds with haematoxylin-eosin. These sarcomas were investigated using a panel of immunohistochemistry and special stains consisting of desmin, smooth muscle actin (SMA), myogenin, S100, mouse macrophages, phosphotungstic acid haematoxylin (PTAH) and Masson's trichrome (MT). All the sarcomas displayed the same histochemical characteristics and a close immunophenotype, characterized by desmin +/-, SMA+, myogenin--, S100--, mouse macrophages + and PTAH-. These tumours thus appear to have similar histologic-type lineage and designation as sarcomas not otherwise specified (NOS) with a large myofibroblastic component appears today to be more appropriate and it is likely to clarify them in the future with the emergence of new markers.

Trichloroethylene Does Not Accelerate Autoimmune Diabetes in NOD Mice.

Pre-existing or contributing risk factors, including genetic predisposition and environmental influences, are largely thought to play a crucial (though ill-elucidated) role in the development of autoimmunity. Trichloroethylene (TCE) is a widely used organic solvent, which has been suspected of increasing the prevalence of autoimmune diseases, e.g., lupus, following environmental contamination. Although few epidemiological data are available, several studies reported an accelerated and more severe disease in TCE-exposed autoimmunity-prone MRL(+/+) mice. To test whether TCE can exert similar deleterious effects on organ-specific autoimmune diseases, non obese diabetic (NOD) mice were given 5 mg/ml TCE via the drinking water for 12 weeks. TCE administration induced a decrease in CD44(+) splenic T-cells and CD45RB(high), CD54(+) blood and splenic T-cells. Conversely, the number of CD45RB(low) splenocytes was increased. Interestingly, the progressive increase in serum TNF-alpha and IFN-gamma levels normally seen with age in these mice was inhibited by TCE. There was also a relative lower incidence of histological changes in the pancreas of TCE-exposed NOD mice than in unexposed mice. Contrary to what has been found in systemic models of autoimmunity, TCE did not accelerate the diabetes of NOD mice and may have a protective effect. This finding suggests that comparative studies using different genetically related autoimmune-prone models are needed to investigate the role of xenobiotics in the precipitation of autoimmunity, particularly in sensitive populations.