Preclinical Evaluation of a Single Intravenous Infusion of hUC-MSC (BX-U001) in Rheumatoid Arthritis.
Preclinical Evaluation of a Single Intravenous Infusion of hUC-MSC (BX-U001) in Rheumatoid Arthritis.
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DOI：
10.1177/0963689720965896
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发表时间：
2020-01
影响因子：
3.3
通讯作者：
Zhao W
中科院分区：
文献类型：
--
作者：
Liu L;Farhoodi HP;Han M;Liu G;Yu J;Nguyen L;Nguyen B;Nguyen A;Liao W;Zhao W
风湿性关节炎（RA）是一种关节炎性疾病，其引起剧烈疼痛和有害炎性细胞因子的过度体循环。目前的治疗是有限的，一些患者反应不佳，一些患者出现严重和有害的副作用。间充质干细胞（MSC）是一种基于细胞的治疗剂，被评估为RA的有效免疫调节剂，可以缓解对基于药物的治疗反应不佳的患者。我们评估了BX-U 001人脐带组织来源的间充质干细胞（hUC-MSC）治疗RA的安全性和有效性，以支持成功的研究性新药申请。用DBA/1 J小鼠建立胶原诱导的类风湿关节炎（CIA）小鼠模型。在原发性RA诱导后24天，给予来自治疗评估组的小鼠尾静脉输注hUC-MSC，而给予对照评估（CA）组小鼠无细胞载体溶液。通过临床评分每天评估所有动物的RA症状，定期采血进行细胞因子分析，并在终点解剖小鼠进行组织学分析。使用线性混合模型比较各组间的变化率。TA组临床评分较CA组明显降低（P < 0.01），显示治疗效果。TA组关节组织学评分显著低于CA组（P < 0.05），但与健康组比较无显著性差异（P > 0.05）。与注射hUC-MSC之前的水平相比，TA组中的（白细胞介素）IL-6的浓度在治疗后2天显著降低了80.0%（P < 0.0001），并且在实验终点时降低了93.4%。对CIA诱导的DBA/1 J小鼠单次静脉输注hUC-MSC（2 × 106个细胞/小鼠）导致RA症状的显著缓解，并且可以在人类中提供显著的治疗益处。
Rheumatoid arthritis (RA) is an inflammatory disease of the joints, which causes severe pain and excessive systemic circulation of harmful inflammatory cytokines. Current treatments are limited, with some patients not responding well, and some experiencing severe and detrimental side effects. Mesenchymal stem cells (MSC) are cell-based therapeutics being evaluated as potent immunomodulators in RA and may provide relief to patients not responding well to drug-based treatments. We evaluated the safety and efficacy of BX-U001 human umbilical cord tissue–derived mesenchymal stem cells (hUC-MSC) to treat RA, in support of a successful investigational new drug application. A collagen-induced arthritis (CIA) mouse model of RA was established in DBA/1 J mice. Mice from the treatment assessment group were given a tail vein infusion of hUC-MSC 24 days after primary RA induction, while control assessment (CA) group mice were given cell-free carrier solution. All animals were evaluated daily for RA symptoms via clinical scoring, blood was taken periodically for cytokine analysis, and mice were dissected at end point for histological analysis. A linear mixed model was used to compare the rate of change among groups. The clinical scores of TA group were significantly reduced compared with CA group (P < 0.01), indicating therapeutic effects. The histological scores of the joints in TA group were significantly lower than those in the CA group (P < 0.05), but had no significant difference compared with Healthy groups (P > 0.05). The concentration of (interleukin) IL-6 in TA group was significantly reduced by 80.0% (P < 0.0001) 2 days after treatment and by 93.4% at the experimental endpoint compared with levels prior to hUC-MSC injection. A single intravenous infusion of hUC-MSC (2 × 106 cells/mouse), to CIA-induced DBA/1 J mice, resulted in significant alleviation of RA symptoms and may provide significant therapeutic benefits in humans.
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影响因子：
4.4
作者：
Paoletti, Audrey;Rohmer, Julien;Mariette, Xavier
通讯作者：
Mariette, Xavier
靶向Notch激活的M1巨噬细胞可减轻炎症性关节炎小鼠模型中的关节组织损伤
DOI：
10.1002/jbmr.3117
发表时间：
2017-07
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Sun W;Zhang H;Wang H;Chiu YG;Wang M;Ritchlin CT;Kiernan A;Boyce BF;Xing L
通讯作者：
Xing L
DOI：
10.1002/art.39692
发表时间：
2016-07
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Hootman JM;Helmick CG;Barbour KE;Theis KA;Boring MA
通讯作者：
Boring MA
影响因子：
64.8
作者：
Culemann, Stephan;Grueneboom, Anika;Kroenke, Gerhard
通讯作者：
Kroenke, Gerhard
影响因子：
168.9
作者：
LeBlanc, Katarina;Frassoni, Francesco;Ringden, Olle
通讯作者：
Ringden, Olle