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同种异体脂肪组织间充质干细胞治疗犬炎症性肠病的安全性和有效性:临床和实验室结果

Safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells for treatment of dogs with inflammatory bowel disease: Clinical and laboratory outcomes.

作者信息

Pérez-Merino E M, Usón-Casaús J M, Zaragoza-Bayle C, Duque-Carrasco J, Mariñas-Pardo L, Hermida-Prieto M, Barrera-Chacón R, Gualtieri M

机构信息

Department of Animal Medicine and Surgery, Veterinary Faculty, University of Extremadura, 10003 Cáceres, Spain.

Department of Animal Medicine and Surgery, Veterinary Faculty, University of Extremadura, 10003 Cáceres, Spain.

出版信息

Vet J. 2015 Dec;206(3):385-90. doi: 10.1016/j.tvjl.2015.08.003. Epub 2015 Aug 7.

DOI:10.1016/j.tvjl.2015.08.003
PMID:26526522
Abstract

Mesenchymal stem cells (MSCs) have shown immunomodulatory and anti-inflammatory effects in experimental colitis, and promising clinical results have been obtained in humans with Crohn's disease and ulcerative colitis. The aim of this study was to determine the safety and feasibility of adipose tissue-derived MSC (ASC) therapy in dogs with inflammatory bowel disease (IBD). Eleven dogs with confirmed IBD received one ASC intravascular (IV) infusion (2 × 10(6) cells/kg bodyweight). The outcome measures were clinical response based on percentage reduction of the validated Clinical Inflammatory Bowel Disease Activity Index (CIBDAI) and Canine Chronic Enteropathy Clinical Activity Index (CCECAI), as well as normalisation of C-reactive protein (CRP), albumin, folate and cobalamin serum concentrations at day 42 post-treatment. The Wilcoxon test was used to compare variables before and after treatment. No acute reaction to ASC infusion and no side effects were reported during follow-up in any dog. Six weeks post-treatment, the CIBDAI and CCECAI decreased significantly and albumin, cobalamin and folate concentrations increased substantially. Differences in CRP concentrations pre- and post-treatment were not significant (P = 0.050). Clinical remission (defined by a reduction of initial CIBDAI and CCECAI >75%) occurred in 9/11 dogs at day 42. The two remaining dogs showed a partial response with reduction percentages of 69.2% and 71.4%. In conclusion, a single IV infusion of allogeneic ASCs was well tolerated and appeared to produce clinical benefits in dogs with severe IBD.

摘要

间充质干细胞(MSCs)在实验性结肠炎中已显示出免疫调节和抗炎作用,并且在患有克罗恩病和溃疡性结肠炎的人类患者中也取得了令人鼓舞的临床结果。本研究的目的是确定脂肪组织来源的间充质干细胞(ASC)治疗犬炎症性肠病(IBD)的安全性和可行性。11只确诊为IBD的犬接受了一次ASC血管内(IV)输注(2×10⁶个细胞/千克体重)。观察指标包括基于经过验证的临床炎症性肠病活动指数(CIBDAI)和犬慢性肠病临床活动指数(CCECAI)降低百分比的临床反应,以及治疗后第42天C反应蛋白(CRP)、白蛋白、叶酸和钴胺素血清浓度的正常化。采用Wilcoxon检验比较治疗前后的变量。在随访期间,没有任何一只犬报告对ASC输注有急性反应或出现副作用。治疗六周后,CIBDAI和CCECAI显著降低,白蛋白、钴胺素和叶酸浓度大幅升高。治疗前后CRP浓度的差异不显著(P = 0.050)。在第42天,11只犬中有9只实现了临床缓解(定义为初始CIBDAI和CCECAI降低>75%)。其余两只犬显示部分反应,降低百分比分别为69.2%和71.4%。总之,单次IV输注同种异体ASCs耐受性良好,似乎对患有严重IBD的犬产生了临床益处。

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