Long-term field safety study evaluating allogeneic, uterine-derived mesenchymal stem cells for refractory feline chronic gingivostomatitis

一项评估异体子宫来源间充质干细胞治疗难治性猫慢性龈口炎的长期现场安全性研究

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Abstract

ObjectivesThe study primarily evaluated the long-term safety of intravenous, allogeneic uterine-derived mesenchymal stromal cells (UMSCs) for client-owned cats affected with refractory feline chronic gingivostomatitis (FCGS). Effectiveness during this long-term extension, when other medications were allowed, was also evaluated.MethodsThis prospective, multisite, open-label extension study evaluated cats with refractory FCGS after partial- or full-mouth extractions and persistent clinical signs despite medical management. During the initial trial, cats received two intravenous doses of 20 million UMSCs 14 days apart. No additional UMSC dosing occurred during the present follow-up period. A total of 35 cats were enrolled through day 365. Safety assessments included physical examination, owner-reported observations and clinicopathology. Clinical outcomes were evaluated descriptively using owner-reported assessment of overall response (ORA) and veterinarian-assessed global oral lesion score (GOLS). Concomitant medications were permitted.ResultsNo serious adverse events (AEs) were associated with UMSC administration, and no clinically relevant abnormalities were observed via hematology or urinalysis. The most common AEs temporally associated with dosing were transient nausea, vomiting, tachypnea, diarrhea, hypersalivation and pyrexia. At 1 year, 69% of cats gained weight (mean increase of 16.2%). Improvement in ORA at days 180 and 365 was 75.8% and 65.6%, respectively. Improvement in GOLS at days 180 and 365 was 51.5% and 46.9%, respectively. Mean reduction in lesion score at 1 year was 33%, with 22% of cats achieving clinical cure. Of the cats, 66% did not restart medical therapy after UMSC treatment, with only 8.6% continuing an immunosuppressant drug.Conclusions and relevanceRepeated intravenous UMSC therapy in cats with refractory FCGS appears safe in the long term, with no reported immunogenic or tumorigenic safety concerns. Clinically meaningful improvements in quality of life were maintained out to 1 year, with concurrent medication use as needed, and most cats were able to discontinue immunosuppressant medications. These results support the safe use of UMSCs for refractory FCGS.

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