Kaur Gagandeep, Ramirez Ana, Xie Chen, Clark David, Dong Charli, Maki Chad, Ramos Thomas, Izadyar Fari, Najera Sandy Oliver Lopez, Harb Jerry, Hao Jijun
College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA, USA.
Animal Dermatology Clinic, Pasadena, CA, USA.
Vet Res Commun. 2022 Feb;46(1):251-260. doi: 10.1007/s11259-021-09853-9. Epub 2021 Oct 29.
Mesenchymal stem cells (MSCs) have emerged as a new therapy for various immune-mediated inflammatory diseases. In this study we perform the first double-blinded, placebo-controlled evaluation of the efficacy of adipose-derived allogenic canine MSCs for the treatment of canine atopic dermatitis (cAD). Enrolled canine patients were randomly divided into placebo (PBS saline), low-dose (5 × 10 cells/kg), and high-dose (5 × 10 cells/kg) treatment groups. Each patient received three subcutaneous MSCs treatments or PBS saline at four-week intervals with injections at five sites. Patients were monitored by physical exams, pruritus visual analog scales (PVAS) signed by the primary caretaker, canine atopic dermatitis extent and severity index-4 (CADESI-4) scores by two veterinarians, and complete blood count and serum chemistry analysis along with laboratory analysis for potential biomarkers. Patients were kept off any immune-modulating drugs during the study period, and oral antibiotics and topicals were used for managing pruritus and secondary infections. The PVAS scores and the serum miR-483 levels were significantly lower in the high dose group compared to the placebo group at day90 post first-treatment. The CADESI-4 scores of the high dose group also showed downward trends. No severe adverse effects were observed in any patient in this study. The high dose MSC treatment is efficacious in alleviating the clinical signs of cAD until 30 days after the last subcutaneous administration of MSCs, and miRNA-483 may be a reliable prognostic biomarker for cAD. The MSCs efficacy and potential biomarkers should be further explored by a larger scale clinical trial.
间充质干细胞（MSCs）已成为治疗各种免疫介导炎症性疾病的一种新疗法。在本研究中，我们首次对异体脂肪来源的犬间充质干细胞治疗犬特应性皮炎（cAD）的疗效进行了双盲、安慰剂对照评估。纳入的犬类患者被随机分为安慰剂组（PBS生理盐水）、低剂量组（5×10⁶细胞/kg）和高剂量组（5×10⁷细胞/kg）。每位患者每隔四周接受三次皮下间充质干细胞治疗或PBS生理盐水治疗，在五个部位进行注射。通过体格检查、由主要护理人员签署的瘙痒视觉模拟量表（PVAS）、两名兽医评定的犬特应性皮炎范围和严重程度指数-4（CADESI-4）评分、全血细胞计数和血清化学分析以及潜在生物标志物的实验室分析对患者进行监测。在研究期间，患者停用任何免疫调节药物，口服抗生素和局部用药用于控制瘙痒和继发感染。首次治疗后90天时，高剂量组的PVAS评分和血清miR-483水平显著低于安慰剂组。高剂量组的CADESI-4评分也呈下降趋势。本研究中未观察到任何患者出现严重不良反应。高剂量间充质干细胞治疗在末次皮下注射间充质干细胞后30天内可有效缓解犬特应性皮炎的临床症状，miRNA-483可能是犬特应性皮炎的可靠预后生物标志物。间充质干细胞的疗效和潜在生物标志物应通过更大规模的临床试验进一步探索。
