Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn's disease: results of a phase I study
Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn's disease: results of a phase I study
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DOI：
10.1136/gut.2010.215152
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发表时间：
2010-12-01
期刊：
影响因子：
24.5
通讯作者：
Hommes, Daniel W.
中科院分区：
文献类型：
--
作者：
Duijvestein, Marjolijn;Vos, Anne Christine W.;Hommes, Daniel W.
背景与目的间充质基质细胞（Mesenchymal stromal cells，MSCs）是一种多能性细胞，在体外和实验性结肠炎中均具有免疫抑制作用。MSC治疗在患有严重的肠道移植物抗宿主病的患者中已经获得了有希望的结果。我们的目的是确定自体骨髓来源的MSC治疗难治性克罗恩病患者的安全性和可行性。患者和干预10例成人难治性克罗恩病患者（8名女性和2名男性）在局部麻醉下进行骨髓穿刺。分离骨髓MSC并离体扩增。在体外测试MSC的表型和功能。9名患者接受了两次剂量1- 2x 106个细胞/kg体重，静脉注射，间隔7天。在随访期间，监测可能的副作用和患者克罗恩病活动指数（CDAI）评分的变化。结肠镜检查进行了在0周和6周，粘膜炎症进行了评估，使用克罗恩病内镜指数severity.Results分离的骨髓间充质干细胞从克罗恩病患者表现出相似的形态，表型和生长潜力相比，骨髓间充质干细胞从健康供体。重要的是，免疫调节能力是完整的，因为克罗恩病MSC在体外显著降低外周血单核细胞增殖。MSC输注没有副作用，除了一名患者可能由于冷冻保存剂DMSO引起的轻度过敏反应外。基线中位CDAI为326（224-378）。三名患者表现出临床反应（CDAI下降>= 70从基线）治疗后6周，相反，三名患者需要手术，由于疾病恶化。结论管理自体骨髓来源的间充质干细胞治疗难治性克罗恩病似乎是安全可行的。在骨髓采集和给药期间未检测到严重不良事件。
Background and aim Mesenchymal stromal cells (MSCs) are pluripotent cells that have immunosuppressive effects both in vitro and in experimental colitis. Promising results of MSC therapy have been obtained in patients with severe graft versus host disease of the gut. Our objective was to determine the safety and feasibility of autologous bone marrow derived MSC therapy in patients with refractory Crohn's disease.Patients and intervention 10 adult patients with refractory Crohn's disease (eight females and two males) underwent bone marrow aspiration under local anaesthesia. Bone marrow MSCs were isolated and expanded ex vivo. MSCs were tested for phenotype and functionality in vitro. 9 patients received two doses of 1-2x10(6) cells/kg body weight, intravenously, 7 days apart. During follow-up, possible side effects and changes in patients' Crohn's disease activity index (CDAI) scores were monitored. Colonoscopies were performed at weeks 0 and 6, and mucosal inflammation was assessed by using the Crohn's disease endoscopic index of severity.Results MSCs isolated from patients with Crohn's disease showed similar morphology, phenotype and growth potential compared to MSCs from healthy donors. Importantly, immunomodulatory capacity was intact, as Crohn's disease MSCs significantly reduced peripheral blood mononuclear cell proliferation in vitro. MSC infusion was without side effects, besides a mild allergic reaction probably due to the cryopreservant DMSO in one patient. Baseline median CDAI was 326 (224-378). Three patients showed clinical response (CDAI decrease >= 70 from baseline) 6 weeks post-treatment; conversely three patients required surgery due to disease worsening.Conclusions Administration of autologous bone marrow derived MSCs appears safe and feasible in the treatment of refractory Crohn's disease. No serious adverse events were detected during bone marrow harvesting and administration.