Case report: Management of generalized infection and draining tracts of the frontomaxillary region in a dog.

Objective: This study aims to report the surgical and medical management of generalized chronic maxillofacial infection with multiple intra- and extraoral draining tracts in a dog. Case summary: A 6 years-old, male neutered pit bull terrier dog underwent a staged procedure. First, a diagnostic work-up including hematologic and biochemical analysis, conventional computed tomography (CT) with contrast of the skull, and a rhinoscopic evaluation of the draining tracts was performed. Samples were obtained for histopathological, microbial, and fungal testing. Second, a 4 week course of antimicrobials based on culture and sensitivity results was administered. Third, an extraoral approach to soft tissue reconstruction was accomplished as a first stage in the repair process. Finally, an intraoral approach to repair the oronasal fistulous draining tracts was performed. A 6 months follow-up skull CT revealed various stages of repair and remodeling and adequate soft tissue healing. Clinical relevance: A staged procedure is a suitable option to treat chronic and generalized frontal and maxillary infection with multiple intra- and extraoral fistulous draining tracts in dogs.

Tilapia Fish Skin Treatment of Third-Degree Skin Burns in Murine Model.

This study explored the feasibility of using fish skin bandages as a therapeutic option for third-degree skin burns. Following the California wildfires, clinical observations of animals with third-degree skin burns demonstrated increased comfort levels and reduced pain when treated with tilapia fish skin. Despite the promises of this therapy, there are few studies explaining the healing mechanisms behind the application of tilapia fish skin. In this study, mice with third-degree burns were treated with either a hydrocolloid adhesive bandage (control) (n = 16) or fish skin (n = 16) 7 days post-burn. Mice were subjected to histologic, hematologic, molecular, and gross evaluation at days 7, 16, and 28 post-burn. The fish skin offered no benefit to overall wound closure compared to hydrocolloids. Additionally, we detected no difference between fish skin and control treatments in regard to hypermetabolism or hematologic values. However, the fish skin groups exhibited 2 times more vascularization and 2 times higher expression of antimicrobial defensin peptide in comparison to controls. Proteomic analysis of the fish skin revealed the presence of antimicrobial peptides. Collectively, these data suggest that fish skin can serve as an innovative and cost-effective therapeutic alternative for burn victims to facilitate vascularization and reduce bacterial infection.

Importance of early diagnosis, multimodal treatment, and a multidisciplinary approach for oral eosinophilic lesions in cats: a retrospective study of 38 cases (1997-2022).

OBJECTIVE: This study aimed to characterize the clinical and histopathologic features of oral eosinophilic lesions in cats. Animals: 38 client-owned cats. METHODS: The medical records database was searched for cats diagnosed with histologically confirmed eosinophilic oral lesions from 1997 to 2022. Information such as medical history, lifestyle factors, clinical presentation, and radiographic and histopathologic features was included for 38 client-owned cats. Response to treatment and long-term follow-up was also recorded. RESULTS: The most affected site was the tongue, with approximately half of the affected cats showing signs of oral discomfort and difficulty eating or breathing. Ulcerative lesions were common, with two-thirds of patients showing more than 1 site affected. Histological samples had a classic appearance, whereas some had an atypical appearance characterized by degenerate collagen clusters associated with multinucleated giant cells. A significant association between lesion location, clinical signs, and prognosis was also found, with patients with palatal lesions being more likely to show respiratory signs and less likely to respond to treatment. Finally, treatment response was observed in most cases within 2 months of commencing therapy combining antimicrobial, and immunosuppressive treatment. CLINICAL RELEVANCE: The results of this study demonstrate the importance of early diagnosis and treatment of cases of oral eosinophilic lesions in cats. Additionally, it emphasizes the need for a multimodal approach to treatment which should include antibacterial therapy. Of no less importance is that other systems may be affected in these patients, warranting a multidisciplinary approach to their management.

Stromal cell therapy in cats with feline chronic gingivostomatitis: current perspectives and future direction.

Feline chronic gingivostomatitis (FCGS) is a painful, immune-mediated, oral mucosal inflammatory disease in cats. The etiology of FCGS remains unclear, with evidence pointing potentially toward a viral cause. Full-mouth tooth extraction is the current standard of care, and cats that are non-responsive to extraction therapy may need lifelong medical management and, in some cases, euthanasia. Adipose-derived mesenchymal stromal cells (adMSCs) have been demonstrated to have advantages in the treatment and potentially the cure of non-responsive FCGS in cats. Therefore, adMSCs have attracted a series of ongoing clinical trials in the past decade. AdMSC therapy immediately after full-mouth tooth extraction was not explored, and we postulate that it may benefit the overall success rate of FCGS therapy. Here, we aim to summarize the current knowledge and impact of adMSCs for the therapeutic management of FCGS and to suggest a novel modified approach to further increase the efficacy of FCGS treatment in cats.

Non-invasive central nervous system assessment of a porcine model of neuropathic pain demonstrates increased latency of somatosensory-evoked potentials.

BACKGROUND: The study of chronic pain and its treatments requires a robust animal model with objective and quantifiable metrics. Porcine neuropathic pain models have been assessed with peripheral pain recordings and behavioral responses, but thus far central nervous system electrophysiology has not been investigated. This work aimed to record non-invasive, somatosensory-evoked potentials (SEPs) via electroencephalography in order to quantitatively assess chronic neuropathic pain induced in a porcine model. NEW METHOD: Peripheral neuritis trauma (PNT) was induced unilaterally in the common peroneal nerve of domestic farm pigs, with the contralateral leg serving as the control for each animal. SEPs were generated by stimulation of the peripheral nerves distal to the PNT and were recorded non-invasively using transcranial electroencephalography (EEG). The P30 wave of the SEP was analyzed for latency changes. RESULTS: P30 SEPs were successfully recorded with non-invasive EEG. PNT resulted in significantly longer P30 SEP latencies (p < 0.01 [n = 8]) with a median latency increase of 14.3 [IQR 5.0 - 17.5] ms. Histological results confirmed perineural inflammatory response and nerve damage around the PNT nerves. COMPARISON WITH EXISTING METHOD(S): Control P30 SEPs were similar in latency and amplitude to those previously recorded invasively in healthy pigs. Non-invasive recordings have numerous advantages over invasive measures. CONCLUSIONS: P30 SEP latency can serve as a quantifiable neurological measure that reflects central nervous system processing in a porcine model of chronic pain. Advancing the development of a porcine chronic pain model will facilitate the translation of experimental therapies into human clinical trials.

Mesenchymal stromal cell therapy for feline chronic gingivostomatitis: Long term experience.

Introduction: Mesenchymal stromal cells (MSC) therapy has emerged as a potential treatment option for refractory FCGS. However, there is a lack of long-term data on the use of MSC therapy in cats. This study aimed to evaluate the long-term safety and efficacy of MSC therapy for FCGS and investigate potential factors associated with treatment outcomes. Methods: This study was a retrospective evaluation of 38 client-owned cats with refractory FCGS who received MSC therapy. Medical records, histopathology, and the Stomatitis Activity Disease Index (SDAI) were reviewed. Correlations of the long-term follow-up success rates with SDAI and cell line type used were conducted. A client survey was also performed to assess side effect occurrence, quality-of-life following treatment, and overall treatment satisfaction. Results: Long-term follow-up ranged from 2 to 9 years post-MSC treatment. The overall positive response rate to MSC treatment was 65.5%, with 58.6% of cats exhibiting permanent improvement or cure. Adverse effects occurring during or immediately after treatment were noted in 34.2% of cases, the majority being transient, self-resolving transfusion-like reactions. No long-term adverse events were noted. No significant correlation in outcome was detected between allogeneic and autologous MSC treatment (p = 0.871) or the severity of the SDAI at entry (p = 0.848) or exit (p = 0.166), or the delta SDAI between entry and exit (p = 0.178). The status 6 months (none to partial improvement vs. substantial improvement to resolution) post-therapy was a predictor of long-term response (value of p < 0.041). Most clients were satisfied with the treatment and outcomes, with 90.6% willing to pursue treatment again, given a similar situation. Discussion: The results of this study support the use of both autologous and allogeneic MSC as an efficacious and safe therapeutic option for refractory FCGS.

Clinical, radiographic and histopathologic features of early-onset gingivitis and periodontitis in cats (1997-2022).

OBJECTIVES: This study aimed to characterize the clinical, radiographic and histopathologic features of early-onset gingivitis (EOG) and periodontitis in cats. METHODS: The medical records database was searched for cats diagnosed with histologically confirmed EOG or periodontitis from 1997 to 2022. Information such as medical history, lifestyle factors, clinical presentation, radiographic and histopathologic features were included for 27 client-owned cats. Response to treatment and long-term follow-up was also recorded. RESULTS: Moderate-to-severe periodontal disease was radiographically confirmed in 78% (21/27) of cats with moderate-to-severe EOG, compared with the evidence of periodontal disease noted in 30% (8/27) of cases during awake oral examination. Horizontal bone loss, along with missing teeth, were the predominant radiographic features noted in 89% (24/27) of cases. The predominant histopathologic feature was moderate-to-severe, erosive-to-ulcerative, neutrophilic and lymphoplasmacytic inflammation with varying degrees of epithelial and stromal hyperplasia. Two cats developed feline chronic gingivostomatitis (FCGS)-like lesions, and seven cats exhibited worsening of aggressive periodontitis (AP). Lack of improvement in the severity of gingivitis or clinical signs evident at the first follow-up appointment was significantly associated with progression of disease (P = 0.004). CONCLUSIONS AND RELEVANCE: The results of this study demonstrate the importance of oral evaluations in cats as early as 6 months of age. For cats exhibiting substantial gingivitis, an anesthetized evaluation, periodontal treatment and long-term monitoring are recommended. Given the high frequency of moderate-to-severe periodontitis encountered in these cats, clients should be informed about the potential need for tooth extractions. EOG may progress to AP. Finally, this study suggests that there could be a link between EOG and FCGS; however, further studies are needed to better characterize this condition and establish any potential link between the two entities.

Metal reactivity is present in dogs with tibial plateau leveling osteotomy and total hip replacement implants.

OBJECTIVE: Determine whether dogs with well-functioning orthopedic metal implants can develop metal reactivity. SAMPLE: Client-owned dogs that had tibial plateau leveling osteotomy (TPLO) or total hip replacement (THR) implants for 12 months or more and control dogs with no implants. PROCEDURES: Lymphocyte transformation testing was performed by exposing peripheral blood lymphocytes to nickel (Ni), chromium (Cr), cobalt (Co), or a combination of these metals. Lymphocyte proliferation was assessed with flow cytometry. Lymphocyte stimulation indexes (SIs) were calculated. A SI > 2 was considered reactive. Median SIs of dogs in response to metal exposure were compared statistically. RESULTS: Samples from 10 dogs with TPLO, 12 dogs with THR, and 7 control dogs were analyzed. Six dogs out of 22 with metal implants had a reactive SI to 1 or more metals, while 2 of 7 control dogs had a SI > 2 when exposed to nickel only. When all metals were considered, no differences in metal reactivity were found between TPLO, THR, and control groups. CLINICAL RELEVANCE: Metal reactivity is present in dogs and can be identified using lymphocyte transformation testing. Reactivity to Ni is present in dogs with and without metal implants. Reactivity to Co and Cr occurs in some dogs with metal implants.

Evaluating the Safety of Intra-Articular Mitotherapy in the Equine Model: A Potential Novel Treatment for Osteoarthritis.

No current treatments available halt osteoarthritis progression in horses or humans. Intra-articular injection of mitochondria is a novel treatment that has the potential to improve cell metabolism and decrease inflammation, but safety of this treatment has yet to be established in the horse. Autologous blood-derived mitochondria isolated using a commercially available kit were injected into the left carpus joint of 3 horses which were monitored for 28 days. Horses received physical examinations, video recorded gait evaluations, joint diameter measurement, synovial fluid collection, and blood collection on day 0 (baseline prior to mitotherapy, day of mitochondria injection), 1, 3, 7, 14, and 28. Systemic inflammation was assessed via complete blood count, fibrinogen, and plasma serum amyloid A (SAA). Local inflammation was assessed via synovial fluid cytology and physical examination parameters. Physical exam parameters remained stable and no joint swelling was observed after mitotherapy. No change was noted in video recorded gait evaluations as determined by a blinded evaluator. Complete blood counts revealed no significant increase in white blood cells. SAA only increased mildly in 1 horse. Fibrinogen became slightly elevated above reference range in 2 horses at day 7, but later normalized. Mild increases in synovial fluid nucleated cell counts and total protein occurred on day 1 and 3, but resolved within 7 days without intervention. Autologous mitochondria injection into the equine intercarpal joint was well tolerated with no signs of inflammation. This safety information allows for future studies evaluating mitotherapy efficacy.

Preliminary evaluation of safety and migration of immune activated mesenchymal stromal cells administered by subconjunctival injection for equine recurrent uveitis.

Introduction: Equine recurrent uveitis (ERU), an immune mediated disease characterized by repeated episodes of intra-ocular inflammation, affects 25% of horses in the USA and is the most common cause of glaucoma, cataracts, and blindness. Mesenchymal stromal cells (MSCs) have immunomodulatory properties, which are upregulated by preconditioning with toll-like receptor agonists. The objective was to evaluate safety and migration of TLR-3 agonist polyinosinic, polycytidylic acid (pIC)-activated MSCs injected subconjunctivally in healthy horses prior to clinical application in horses with ERU. We hypothesized that activated allogeneic MSCs injected subconjunctivally would not induce ocular or systemic inflammation and would remain in the conjunctiva for >14 days. Methods: Bulbar subconjunctiva of two horses was injected with 10 × 106 pIC-activated (10 µg/mL, 2 h) GFP-labeled MSCs from one donor three times at two-week intervals. Vehicle (saline) control was injected in the contralateral conjunctiva. Horses received physical and ophthalmic exams [slit lamp biomicroscopy, rebound tonometry, fundic examination, and semiquantitative preclinical ocular toxicology scoring (SPOTS)] every 1-3 days. Systemic inflammation was assessed via CBC, fibrinogen, and serum amyloid A (SAA). Horses were euthanized 14 days following final injection. Full necropsy and histopathology were performed to examine ocular tissues and 36 systemic organs for MSC presence via IVIS Spectrum. Anti-GFP immunohistochemistry was performed on ocular tissues. Results: No change in physical examinations was noted. Bloodwork revealed fibrinogen 100-300 mg/dL (ref 100-400) and SAA 0-25 µg/mL (ref 0-20). Ocular effects of the subjconjucntival injection were similar between MSC and control eyes on SPOTS grading system, with conjunctival hypermia, chemosis and ocular discharge noted bilaterally, which improved without intervention within 14 days. All other ocular parameters were unaffected throughout the study. Necropsy and histopathology revealed no evidence of systemic inflammation. Ocular histopathology was similar between MSC and control eyes. Fluorescent imaging analysis did not locate MSCs. Immunohistochemistry did not identify intact MSCs in the conjunctiva, but GFP-labeled cellular components were present in conjunctival phagocytic cells. Discussion: Allogeneic pIC-activated conjunctival MSC injections were well tolerated. GFP-labeled tracking identified MSC components phagocytosed by immune cells subconjunctivally. This preliminary safety and tracking information is critical towards advancing immune conditioned cellular therapies to clinical trials in horses.

A Fresh Glimpse into Cartilage Immune Privilege.

The increasing prevalence of degenerative cartilage disorders in young patients is a growing public concern worldwide. Cartilage's poor innate regenerative capacity has inspired the exploration and development of cartilage replacement treatments such as tissue-engineered cartilages and osteochondral implants as potential solutions to cartilage loss. The clinical application of tissue-engineered implants is hindered by the lack of long-term follow-up demonstrating efficacy, biocompatibility, and bio-integration. The historically reported immunological privilege of cartilage tissue was based on histomorphological observations pointing out the lack of vascularity and the presence of a tight extracellular matrix. However, clinical studies in humans and animals do not unequivocally support the immune-privilege theory. More in-depth studies on cartilage immunology are needed to make clinical advances such as tissue engineering more applicable. This review analyzes the literature that supports and opposes the concept that cartilage is an immune-privileged tissue and provides insight into mechanisms conferring various degrees of immune privilege to other, more in-depth studied tissues such as testis, eyes, brain, and cancer.

Management of bilateral pterygoid myositis ossificans-like lesion in dogs.

Myositis ossificans (MO) and myositis ossificans-like lesions have been rarely described within the veterinary literature, and are even less common in the maxillofacial region. When MO affects the muscles of mastication, it can result in complete or partial inability to open the mouth. As with other conditions resulting in decreased or restricted mandibular range of motion, severe and potentially fatal sequelae such as difficulty with prehension, swallowing, and air exchange are possible. Diagnostic imaging is essential in achieving an accurate diagnosis and in formulating an appropriate treatment plan. In this "method" manuscript, we provide a detailed description of our approach to diagnosis and surgical management of MO-like lesions of the pterygoid muscles and describe our experience with two young French bulldogs.

A Retrospective Study on Mandibular Reconstruction Following Excision of Canine Acanthomatous Ameloblastoma.

The successful excision of a locally invasive tumor such as canine acanthomatous ameloblastoma (CAA) typically results in a mandibular contour-derforming, critical-size defect that alters the jaw kinematics, and may affect the patient's quality of life. In this case series, we describe our experience using the regenerative approach of a titanium locking plate and compression resistant matrix infused with rhBMP-2 for the immediate or delayed reconstruction following mandibulectomy for the excision of mandibular CAA in 11 dogs. Surgical planning included computed tomography (CT), with and without contrast, in all cases, and 3D-printed models in four cases. Tumor-free surgical margins were achieved in all dogs. Clinical and diagnostic imaging follow-up (mean, 23.1 months) were performed in-person (11 cases) and with CT/cone-beam computed tomography in most cases, with standard radiography (3 cases) and telemedicine being utilized in 5 cases. At 2 weeks postoperatively, hard tissue was palpable at the defect. Follow-up imaging at 1 month postoperatively revealed evidence of bridging new bone with a heterogeneous appearance, that remodeled over 3-6 months to bone of a similar size, shape and trabecular pattern as native bone. Histological evaluation of regenerated bone was available in two cases, and was supportive of our clinical and imaging findings of normal remodeled bone. Clinically, all dogs returned to a normal lifestyle, rapidly resumed eating and drinking, and exhibited normal occlusion. Complications included wound dehiscence in one dog and self-limiting exuberant bone formation in two dogs. Tumor regrowth, failure of the implant or fracture of the regenerated bone were not observed. We conclude that the mandibular reconstruction using a regenerative approach is safe, feasible, and results in restoration of mandibular contour in dogs following segmental and bilateral rostral mandibulectomy for benign but invasive oral tumors such as CAA.

The oromaxillofacial region as a model for a one-health approach in regenerative medicine.

The concept of a one-health approach in regenerative medicine has gained tremendous momentum in the scientific and public communities in recent years. Knowledge derived from this approach informs innovative biomedical research, clinical trials, and practice. The ultimate goal is to translate regenerative strategies for curing diseases and improving the quality of life in animals and people. Building and fostering strong and enthusiastic interdisciplinary and transdisciplinary collaboration between teams with a wide range of expertise and backgrounds is the cornerstone to the success of the one-health approach and translational sciences. The veterinarian's role in conducting clinical trials in client-owned animals with naturally occurring diseases is critical and unique as it may potentially inform human clinical trials. The veterinary regenerative medicine and surgery field is on a steep trajectory of discoveries and innovations. This manuscript focuses on oromaxillofacial-region regeneration to exemplify how the concept of interdisciplinary and transdisciplinary collaboration and the one-health approach influenced the authors' work experience at the University of California-Davis.

Tissue Engineering of Canine Cartilage from Surgically Debrided Osteochondritis Dissecans Fragments.

This study in dogs explored the feasibility of using cartilage fragments removed and discarded during routine palliative surgery for osteochondritis dissecans (OCD) as a source of primary chondrocytes for scaffold-free cartilage tissue-engineering. Primary chondrocytes were obtained from three OCD donors and one age-matched healthy articular cartilage (HAC) donor. After monolayer expansion of primary cells, a three-dimensional spherical suspension culture was implemented. Following this stage, cells were seeded at a high density into custom-made agarose molds that allowed for size and shape-specific constructs to be generated via a method of cellular self-assembling in a scaffold-free environment. Fifty-eight neocartilage constructs were tissue-engineered using this methodology. Neocartilage constructs and native cartilage from shoulder joint were subjected to histological, mechanical, and biochemical testing. OCD and HAC chondrocytes-sourced constructs had uniformly flat morphology and histology consistent with cartilage tissue. Constructs sourced from OCD chondrocytes were 1.5-times (32%) stiffer in compression and 1.3 times (23%) stronger in tension than constructs sourced from HAC chondrocytes and only 8.7-times (81%) less stiff in tension than native tissue. Constructs from both cell sources consistently had lower collagen content than native tissue (22.9%/dry weight [DW] for OCD and 4.1%/DW for HAC vs. 51.1%/DW native tissue). To improve the collagen content and mechanical properties of neocartilage, biological and mechanical stimuli, and thyroid hormone (tri-iodothyronine) were applied to the chondrocytes during the self-assembling stage in two separate studies. A 2.6-fold (62%) increase in compressive stiffness was detected with supplementation of biological stimuli alone and 5-fold (81%) increase with combined biological and mechanical stimuli at 20% strain. Application of thyroid hormone improved collagen content (1.7-times, 33%), tensile strength (1.8-times, 43%), and stiffness (1.3-times, 21%) of constructs, relative to untreated controls. Collectively, these data suggest that OCD chondrocytes can serve as a reliable cell source for cartilage tissue-engineering and that canine chondrocytes respond favorably to biological and mechanical stimuli that have been shown effective in chondrocytes from other animal species, including humans.

The Diagnostic Yield of Cone-Beam Computed Tomography for Degenerative Changes of the Temporomandibular Joint in Dogs.

Degenerative changes of the temporomandibular joint (DTMJ) may be diagnosed via cone - beam computed tomography (CBCT). However, despite advancement in CBCT imaging, correlation of DTMJ features identified on CBCT with gross and histological findings is currently limited. This study aimed to correlate CBCT findings of DTMJ of dogs with gross and histopathologic changes. Temporomandibular joints (TMJ) (n = 38) from fresh cadaver heads of asymptomatic dogs (n = 19) were examined radiologically, macroscopically, and microscopically. Association of CBCT - detected DTMJ changes with gross and histological findings were statistically evaluated via kappa statistics and ordinal logistic mixed-effects models. The radiological changes observed on CBCT included joint space narrowing, subchondral/cortical bone changes (i.e., erosions or lysis), osteophytes, and subchondral bone sclerosis. Upon macroscopic evaluation, the majority of examined specimens had mild changes with cartilage defects and osteophytes affecting <10% of the total articular surface area. Histopathologic changes comprised splitting and degeneration of the fibrous cartilage layers, subchondral bone exposure, subchondral bone sclerosis, focal subchondral bone lysis, and occasional cell death. Subchondral sclerosis was the most prevalent finding radiologically and histologically with a fair to excellent agreement. Importantly, the more severe the TMJ degenerative changes, the higher the agreement between CBCT and histology. Based on the correlative results of statistical analysis, CBCT was found to be a suitable modality to evaluate DTMJ.

Management of Septic Arthritis of the Temporomandibular Joint in Dogs.

Septic arthritis of the temporomandibular joint (TMJ) in dogs and other mammals is a rare condition. It is typically associated with notable pain, swelling, and difficulty in opening the mouth. Unlike degenerative TMJ disease, septic arthritis requires urgent intervention. The etiology of the condition may include penetrating trauma, an extension of local infection, such as otitis media, or the hematogenous spread of a pathogen. However, the precise cause may not always be identified. Diagnostic imaging with Computed Tomography (CT), cone-beam CT (CBCT), and/or Magnetic Resonance Imaging (MRI) are helpful for honing the definitive diagnosis and formulating a treatment plan. Subsequently, exploratory surgery may be required to obtain samples for culture and sensitivity and histology and to lavage the joint. In this "methods" article, we provide a detailed description of our approach to diagnosis and management of septic TMJ arthritis in four dogs.

Adult Dermal Stem Cells for Scaffold-Free Cartilage Tissue Engineering: Exploration of Strategies.

Dermis-isolated adult stem (DIAS) cells, abundantly available, are attractive for regenerative medicine. Strategies have been devised to isolate and to chondroinduce DIAS cells from various animals. This study aimed to characterize DIAS cells from human abdominal skin (human dermis-isolated adult stem [hDIAS] cells) and to compare and to refine various chondroinduction regimens to form functional neocartilage constructs. The stemness of hDIAS cells was verified (Phase I), three chondroinduction pretreatments were compared (Phase II), and, from these, one regimen was carried forward for refinement in Phase III for improving the mechanical properties of hDIAS cell-derived constructs. Multilineage differentiation and mesenchymal stem cell markers were observed. Among various chondroinduction pretreatments, the nodule formation pretreatment yielded constructs at least 72% larger in diameter, with higher glycosaminoglycan (GAG) content by 44%, compared with other pretreatments. Furthermore, it was found that culturing cells on nontissue culture-treated surfaces yielded constructs (1) on par with constructs derived from aggrecan-coated surfaces and (2) with superior mechanical properties than constructs derived from cells cultured on tissue culture-treated surfaces. After the nodule formation pretreatment, combined supplementation of TGF-ß1, IGF-I, and fetal bovine serum significantly enhanced aggregate modulus and shear modulus by 75% and 69%, respectively, over the supplementation by TGF-ß1 alone. In summary, human skin-derived DIAS cells are responsive to chondroinduction for forming neocartilage. Furthermore, the mechanical properties of the resultant human constructs can be improved by treatments shown to be efficacious in animal models. Advances made toward tissue-engineering cartilage using animal cells were shown to be applicable to hDIAS cells for cartilage repair and regeneration.

A nephrotoxicity-free, iron-based contrast agent for magnetic resonance imaging of tumors.

Gadolinium-based contrast agents (GBCAs) are the most widely used T1 contrast agents for magnetic resonance imaging (MRI) and have achieved remarkable success in clinical cancer diagnosis. However, GBCAs could cause severe nephrogenic systemic fibrosis to patients with renal insufficiency. Nevertheless, GBCAs are quickly excreted from the kidneys, which shortens their imaging window and prevents long-term monitoring of the disease per injection. Herein, a nephrotoxicity-free T1 MRI contrast agent is developed by coordinating ferric iron into a telodendritic, micellar nanostructure. This new nano-enabled, iron-based contrast agent (nIBCA) not only can reduce the renal accumulation and relieve the kidney burden, but also exhibit a significantly higher tumor to noise ratio (TNR) for cancer diagnosis. In comparison with Magnevist (a clinical-used GBCA), Magnevist induces obvious nephrotoxicity while nIBCA does not, indicating that such a novel contrast agent may be applicable to renally compromised patients requiring a contrast-enhanced MRI. The nIBCA could precisely image subcutaneous brain tumors in a mouse model and the effective imaging window lasted for at least 24 h. The nIBCA also precisely highlights the intracranial brain tumor with high TNR. The nIBCA presents a potential alternative to GBCAs as it has superior biocompatibility, high TNR and effective imaging window.

Histological, Immunological, and Genetic Analysis of Feline Chronic Gingivostomatitis.

Feline chronic gingivostomatitis (FCGS) is an immune-mediated inflammatory condition affecting the oral mucosa that results in substantial pain and suffering. The goal of this study was to complete an in-depth immunohistochemistry analysis of affected FCGS mucosa, to perform and compare immune cell phenotypes in the blood of FCGS and healthy controls cats, and to determine a transcriptomic profile of the affected and normal oral mucosa of FCGS cats. We hypothesized that cats with FCGS would have circulating activated CD8+ T cells and that tissues would be infiltrated with activated B and T cells with a highly proinflammatory transcriptome. We found that oral mucosal tissues from cats with FCGS have high tissue infiltration of B cells and that T cells include both CD4+ and CD8+ lymphocytes. Cells positive for CD25 (IL2 receptor, indicative of lymphocyte activation) and FOXP3 (indicative of regulatory T cells) were scattered throughout the mucosa. Compared to healthy individuals, cats with FCGS had high circulating CD8+ effector memory cells with a concurrent decrease in central memory cells and evidence of circulating activated CD8+ T cells (CD25+, CD62L-). Gene expression in the affected tissues was enriched for genes associated with T-cell signaling, cell adhesion molecules, leukocyte migration, inflammatory signaling pathways, extracellular matrix-receptor interactions, cytokine-cytokine receptor interactions, and natural killer cell-mediated cytotoxicity, among others. These data are essential to understand disease pathogenesis, to inform mechanism of action studies for future and current therapies, and to help select prognostic biomarkers and potency assays for stem cell treatment of FCGS.