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Topical Allogeneic Adipose-Derived Mesenchymal Stem Cell Therapy in Canine Keratoconjunctivitis Sicca
canine keratoconjunctivitis sicca,allogenic,adipose-derived stem cells,eye drops,
|Publication Year :||2019|
In the past two decades, mesenchymal stem cells have been tested in the treatment of various diseases and tissue regeneration. Among these mesenchymal stem cells have gradually gained much attention because of their availability, stability, safety, low-ethical issue and with wide ranges of potential therapeutic applications. Bone marrow-derived mesenchymal stem cells were found and used earlier, so the bulk of early studies used them. However, adipose-derived stem cells are much easier to access and can be acquired in a large quantity. Especially when the euthanasia of stray animals was banned in Taiwan after early 2017, it is even more difficult to obtain bone marrow from dogs. That is why we chose canine adipose-derived mesenchymal stem cells (cAD-MSCs) as the research subjects with potential future applications.
Canine keratoconjunctivitis sicca (KCS) is thought to be an immune-mediated disease, therefore canine KCS patients provide a useful model of autoimmune-mediated diseases. Current therapy of canine KCS mainly uses immunosuppressants, but the effectiveness was limited in some patients. In the past three years, some studies showed the results of the use of mesenchymal stem cells in treating canine KCS via periocular injections. However, the periocular injection procedure requires sedation or general anesthesia, and may lead to iatrogenic or incidental injury during the injection process. The aim of this study was to investigate the efficacy of topical allogenic adipose-derived stem cells in clinical patients of canine KCS.
First, adipose-derived stem cells were isolated and confirmed for their capability of differentiation and immunomodulatory properties. In addition, preparation methods for eye drops of cAD-MSCs was developed and its optimal preservation was tested. Secondly, canine KCS patients were included and divided into two groups based on history of previous therapy for clinical trial. All patients received topical canine adipose-derived mesenchymal stem cells (cAD-MSCs) therapy weekly for 6 consecutive weeks and complete ophthalmic examinations were performed at baseline and 3rd, 6th, 9th week, respectively. A complete ophthalmic examination included Schirmers tear test-1 (STT-1), tear break-up time(TBUT), fluorescein stain, tear osmolarity measurement by i-PEN and assessments the severity of clinical signs such as mucoid discharge, conjunctival hyperemia, and corneal changes.
Based on the results of the clinical trials, the quantity and quality of tears have improved significantly following topical cAD-MSCs treatment. More than half of the patients were found improved in the tear quantity. In particular, 56.5% of the patients that were unresponsive to prior immunosuppressant therapy had an effective increase in tear volume. As relieved from symptoms and uncomfortable, patients’ quality of life was improved following treatment. Based on these results, weekly administration of cAD-MSCs for six consecutive weeks may serve as a good alternative to cyclosporine A or tacrolimus for treatment of canine KCS. Topical cAD-MSCs therapy requires once weekly for six times. It’s much easier for dog owners when compared with traditional treatment, that required frequent administration with two to three times daily. To sum up, topical cAD-MSCs may be beneficial especially in KCS patients with poor owner compliance for frequent daily use of eye drops or those who are unresponsive to immunosuppressant therapy.
|Appears in Collections:||臨床動物醫學研究所|
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