Targeting Improves MSC Treatment of Inflammatory Bowel Disease
Targeting Improves MSC Treatment of Inflammatory Bowel Disease
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DOI：
10.1038/mt.2010.54
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发表时间：
2010-07-01
影响因子：
12.4
通讯作者：
Dennis, James E.
中科院分区：
文献类型：
--
作者：
Ko, In Kap;Kim, Byung-Gyu;Dennis, James E.
炎症性肠病（IBD），包括克罗恩病和溃疡性结肠炎，是一种以t细胞浸润到结肠为特征的炎症性自身免疫性疾病。间充质干细胞（MSCs）由于其免疫抑制能力而具有拯救IBD的潜力，临床研究显示其对肠移植物抗宿主病有积极作用。我们在这里展示了一种新的方法，将MSCs包裹上针对寻址蛋白的抗体，以增强其向结肠的递送，从而提高治疗效果。生物发光成像（BLI）表明，与未处理的MSCs、Ab（同种型）-MSCs和Ab(MAdCAM)-MSCs相比，血管细胞粘附分子抗体（Ab）包被的MSCs （Ab(VCAM-1)-MSCs）对炎症肠系膜淋巴结（MLN）和结肠的递送效率最高。在治疗方面，与仅注射MSCs、同种型Ab、游离Ab + MSCs或仅注射载体对照的小鼠相比，当IBD小鼠注射address - sin Ab-coated MSCs时，它们的存活率显着提高，IBD治疗评分更高，体重增加显著改善。这些数据表明，MSC上的抗寻址蛋白Ab涂层增加了细胞向炎症结肠的递送，提高了MSC治疗IBD的疗效。这是第一个研究表明，当干细胞首先被特异性靶向炎症部位的抗体包裹时，治疗效果会增加。
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is an inflammatory autoimmune disease characterized by T-cell infiltration to the colon. Mesenchymal stem cells (MSCs) have the potential to rescue IBD owing to their immunosuppressive capabilities and clinical studies have shown positive influence on intestinal graft versus host disease. We demonstrate here a new method to coat MSCs with antibodies against addressins to enhance their delivery to the colon and thereby increase the therapeutic effectiveness. Bioluminescence imaging (BLI) demonstrated that vascular cell adhesion molecule antibody (Ab)-coated MSCs (Ab(VCAM-1)-MSCs) had the highest delivery efficiency to inflamed mesenteric lymph node (MLN) and colon compared to untreated MSCs, Ab(isotype)-MSCs, and Ab(MAdCAM)-MSCs. Therapeutically, when mice with IBD were injected with addressin Ab-coated MSCs, they showed dramatically improved survival rates, higher IBD therapeutic scores, and significantly improved body weight gain compared to mice injected with MSCs only, isotype Ab, free Ab plus MSCs, or vehicle-only controls. These data demonstrate that anti-addressin Ab coating on MSC increased cell delivery to inflamed colon and increased the efficacy of MSC treatment of IBD. This is the first study showing an increased therapeutic efficacy when stem cells are first coated with antibodies specifically target them to inflamed sites.