Department of Colorectal Surgery, Cleveland Clinic, Ohio, USA.
Curr Opin Gastroenterol. 2019 Jul;35(4):311-320. doi: 10.1097/MOG.0000000000000545.
Perianal Crohn's disease is a morbid and disabling condition, notoriously difficult to successfully treat with conventional medical and surgical therapies. Mesenchymal stem cells (MSCs) are an emerging novel therapy for perianal Crohn's disease.
Over 300 patients with perianal Crohn's disease have now been treated with MSCs in the context of clinical trials. All trials have demonstrated safety, and efficacy superior to conventional therapy with biologics and surgical intervention. This was consistent despite the heterogeneity in study protocols including variability in cell dosing, mode of delivery, repeat dosing, and allogeneic versus autologous donors. Sustained healing to 1 year has also been demonstrated in a recent extension of the largest phase III study confirming superior efficacy of MSCs to placebo at 1-year follow-up. However, several outstanding questions regarding the use of MSCs for perianal Crohn's disease remain, which, if answered, could enhance MSCs' treatment efficacy. These include defining the optimal MSC donor, optimal MSC source (e.g., bone marrow versus adipose tissue), investigating a potential alloimmune response following allogeneic cellular delivery, and determining the optimal mode for MSC delivery. In addition to these unanswered questions, significant challenges in the required infrastructure and cost required for cell-based therapies may drive future research toward identifying novel acellular therapies.
Novel regenerative therapies offer promising new treatment options for perianal Crohn's disease, without the risk of opportunistic infection seen with biologics and incontinence with surgical techniques. Future research will help define the optimal MSC product and treatment protocol, and may even expand our horizon of regenerative medicine into acellular therapy as well as cell-based therapies.
肛周克罗恩病是一种严重的致残性疾病，传统的医学和手术治疗方法很难成功治疗。间充质干细胞（MSCs）是治疗肛周克罗恩病的一种新兴的新型治疗方法。
目前已有 300 多名肛周克罗恩病患者在临床试验中接受了 MSCs 的治疗。所有试验均证明了安全性，并且疗效优于生物制剂和手术干预的常规治疗。尽管研究方案存在异质性，包括细胞剂量、给药方式、重复剂量和同种异体与自体供体的差异，但结果都是一致的。最近一项最大的 III 期研究的扩展证实，MSCs 在 1 年随访时的疗效优于安慰剂，具有持续 1 年的愈合效果。然而，关于 MSCs 治疗肛周克罗恩病仍存在几个悬而未决的问题，如果这些问题得到解答，可能会提高 MSCs 的治疗效果。这些问题包括确定最佳的 MSC 供体、最佳的 MSC 来源（例如骨髓与脂肪组织）、研究同种异体细胞输送后的潜在同种免疫反应，以及确定 MSC 输送的最佳方式。除了这些未解答的问题外，细胞治疗所需的基础设施和成本方面的重大挑战可能会促使未来的研究朝着确定新型无细胞治疗的方向发展。
新型再生疗法为肛周克罗恩病提供了有前途的新治疗选择，没有生物制剂治疗的机会性感染风险，也没有手术技术导致的失禁风险。未来的研究将有助于确定最佳的 MSC 产品和治疗方案，甚至可能将我们的再生医学视野扩展到无细胞治疗以及细胞治疗。
