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

IntroductionMesenchymal 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.MethodsThis 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.ResultsLong-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.DiscussionThe results of this study support the use of both autologous and allogeneic MSC as an efficacious and safe therapeutic option for refractory FCGS

Fracture Limits of Maxillary Fourth Premolar Teeth in Domestic Dogs Under Applied Forces

A cadaveric study was performed to investigate the external mechanical forces required to fracture maxillary fourth premolar teeth in domestic dogs and describe a clinically relevant model of chewing forces placed on functionally important teeth in which fracture patterns are consistent with those defined by the American Veterinary Dental College (AVDC). Twenty-four maxillary fourth premolar teeth were harvested from dog cadavers. Samples consisted of teeth with surrounding alveolar bone potted in polycarbonate cylinders filled with acrylic. The cylinders were held by an aluminum device at an angle of 60° with respect to the ground. An axial compression test was performed, creating a force upon the occluso-palatal aspects of the main cusps of the crowns of the teeth. The highest compressive force prior to failure was considered the maximum force sustained by the teeth. Results showed the mean maximum force (± SD) sustained by the tested teeth at the point of fracture was 1,281 N (± 403 N) at a mean impact angle (± SD) of 59.7° (± 5.2°). The most common fracture type that occurred among all samples was a complicated crown fracture (n = 12), followed by an uncomplicated crown fracture (n = 6), complicated crown-root fracture (n = 5), and uncomplicated crown-root fracture (n = 1). There was no statistically significant correlation between dog breed, age, weight, impact angle, crown height or crown diameter, and the maximum force applied at the point of fracture. The only independent variable that remained significantly associated with maximum force was the crown height to diameter ratio (p = 0.005), suggesting that a decreased ratio increases tooth fracture resistance. The methodology described herein has been successful in creating a pattern of fracture of maxillary fourth premolar teeth consistent with that defined by the AVDC under angled compression at forces within the maximum chewing capability of the average domestic dog

Failure of regression of the cranial gonadal suspensory ligament in a 3 year old male Quarter Horse

Cryptorchidism is the most common developmental defect in the horse (Schambourg, M.A. et al, 2006). Studies have shown 2-8% prevalence for this condition in horses. Cryptorchidism is characterized by failure of one or both testes to descend into the scrotum. Retained testes can be found anywhere between the caudal poles of the kidneys to subcutaneously outside of the body wall, but abdominal retention is the most common presentation (Amann, R.P. and Veeramachaneni, D.N.R., 2007). Normal and disturbed testicular descent is frequently approached exclusively through consideration of the caudal testicular suspensory apparatus. However, embryological gonads develop with both cranial and caudal suspensory ligaments, and the sexes differ in respect to the persistence and development of both the cranial and caudal ligaments (Van Der Schoot, P. and Elger, W., 1992). The following case report illustrates an atypical case of bilateral abdominal cryptorchidism. "Starham's Yellow Brick", a 3 year old male Quarter Horse that presented to the Cornell University Hospital for Animals for persistence of stallion-like behavior despite previously reported castration. Upon physical examination, testes could not be seen or palpated within the scrotum. After performing an hCG stimulation test and measuring testosterone, the diagnosis of cryptorchidism was made. Laparoscopic abdominal exploratory with the horse in dorsal recumbency was unsuccessful in locating the testis. Bilateral exploratory flank celiotomies were then performed and the testes were located and removed from an unusual anatomical position

Feline chronic gingivostomatitis current concepts in clinical management.

Practical relevanceFeline chronic gingivostomatitis (FCGS) is a debilitating disease for cats and a challenge for veterinarians and cat caregivers alike. Recent literature indicates that the disease is immune-mediated in nature and likely associated with a chronic viral infection in patients with higher alpha diversity of their subgingival microbiome. The immune-mediated nature of FCGS includes both local as well as systemic effects, and the transcriptomic analysis of affected patients supports these findings.Treatment optionsLocalized therapy in the form of surgical extraction of all, or nearly all, teeth continues to be the mainstay of treatment. For cats that do not respond to surgical management, medical management, in the form of immunosuppressive or immunomodulatory therapy, remains an option. Analgesia is of fundamental importance. Immunomodulation utilizing mesenchymal stromal cell therapy provides an alternative treatment avenue for refractory patients and likely targets the chronic viral infection present in this disease. The potential for treatment stratification and use of novel systemic treatment options may be revealed as the molecular pathways involved in this disease are better described.AimsThis review outlines current and emerging concepts linking available science pertaining to FCGS and clinical management of the disease.Evidence baseThe article draws on the best evidence base at this juncture and is also driven by the authors' collective experience of working on the disease for over a decade

Distinctive characteristics of extracellular vesicles from feline adipose and placenta stromal cells unveil potential for regenerative medicine in cats.

ObjectiveExtracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) are promising avenues in regenerative medicine, offering unique immunomodulatory and regenerative properties with lower immunogenicity. This study delves into the distinctive features of EVs extracted from feline adipose-derived MSCs (ASCs) and placenta-derived MSCs (PMSCs). The tissues were collected from 11 female cats aged between 4 and 7 years old.SampleEVs extracted from MSCs from discarded fetal membranes from 7 female cats and SC adipose tissue from 11 cats.MethodsWe comprehensively explored morphological characteristics, mitochondrial density, surface markers, and pro- and anti-inflammatory mediators, uncovering notable differences between ASCs and PMSCs.ResultsMorphologically, ASCs exhibit a spindle-shaped form in contrast to the spherical morphology of PMSCs. Proliferation and clonogenic potential assessments reveal the faster proliferation and robust clonogenic nature of ASCs, suggesting their potential vital role in regenerative processes. Surface marker expression analysis indicates a significantly higher expression of multipotency-associated markers in ASCs, suggesting their superior proregenerative potential. Phenotyping of EVs demonstrates distinctive features, with CD9 expression suggesting varied EV secretion patterns. Notably, PMSCs exhibit superior CD81 expression, indicating their potential as preferred donors of mitochondria. Pro- and anti-inflammatory mediators analyzed at mRNA and microRNA levels reveal higher RNA content in EVs compared to source cells, emphasizing the potential of EVs in directing regenerative processes. Differential microRNA expression in EVs derived from ASCs hints at their regulatory roles in anti-inflammatory and immunometabolic processes.Clinical relevanceThis study lays a foundation for understanding the nuances between ASCs and PMSCs, which is crucial for harnessing the full therapeutic potential of MSCs and their EVs in tissue repair and regeneration