Gastroenterology Department, Hospital Clinic, Barcelona, Spain.
Dig Dis. 2012;30(4):387-91. doi: 10.1159/000338134. Epub 2012 Jul 12.
Cellular therapy is a promising new approach to address unmet medical needs in patients with IBD, mainly Crohn's disease (CD). Two series have reported autologous hematopoietic stem cell transplantation (HSCT) for CD. The largest one is a phase I study from Chicago including 24 patients with active CD refractory to conventional therapies. All patients went into remission with a CD Activity Index (CDAI) <150. The percentage of clinical relapse-free survival was 91% at 1 year, 63% at 2 years, 57% at 3 years, 39% at 4 years and 19% at 5 years. The percentage of patients in remission (CDAI <150), steroid-free or medication-free at any post-transplantation evaluation interval remained ≥70, ≥80 and ≥60%, respectively. In Europe and Canada, a currently ongoing randomized trial hopes to answer the question of whether autologous HSCT adds any benefit to the effect of immunosuppression used during mobilization. Although promising, HSCT for CD is still experimental and its toxicity leaves this option for a considerably reduced number of refractory patients in whom the disease is not amenable to surgical resection. A more recently developed, less aggressive approach involves the use of mesenchymal stem cells (MSCs). Successful pre-clinical studies using MSCs in models of autoimmunity, inflammation or tissue damage have paved the way for clinical trials. Two phase I studies on autologous bone marrow-derived MSCs for the treatment of active refractory CD have been published recently; one using systemic administration in patients with luminal CD and the other assessing the effects of local injection of MSCs for the treatment of fistulizing CD, showing that application of autologous MSCs is feasible, well tolerated and might produce clinical benefits.
细胞治疗是一种有前途的新方法，可以解决 IBD 患者未满足的医疗需求，主要是克罗恩病（CD）。有两个系列报道了自体造血干细胞移植（HSCT）治疗 CD。其中最大的一项是来自芝加哥的一项 I 期研究，包括 24 例对常规治疗无效的活动期 CD 患者。所有患者的 CD 活动指数（CDAI）<150，均进入缓解期。1 年时无临床复发存活率为 91%，2 年时为 63%，3 年时为 57%，4 年时为 39%，5 年时为 19%。任何移植后评估间隔的缓解（CDAI<150）、无类固醇或无药物治疗的患者比例分别保持在≥70%、≥80%和≥60%。在欧洲和加拿大，目前正在进行一项随机试验，旨在回答自体 HSCT 是否能增加动员期间免疫抑制的效果。尽管有希望，但 CD 的 HSCT 仍然是实验性的，其毒性使这一选择仅限于少数无法手术切除的难治性患者。一种最近开发的、侵袭性较小的方法涉及间充质干细胞（MSCs）的使用。在自身免疫、炎症或组织损伤模型中使用 MSCs 的成功临床前研究为临床试验铺平了道路。最近发表了两项关于自体骨髓源性 MSCs 治疗活动期难治性 CD 的 I 期研究；一项研究在腔 CD 患者中进行全身给药，另一项研究评估局部注射 MSCs 治疗瘘 CD 的效果，表明应用自体 MSCs 是可行的、耐受良好的，并且可能产生临床获益。
