一项关于同种异体骨髓来源间充质干细胞体外扩增用于治疗儿童肛周瘘管型克罗恩病的 I 期研究。

A Phase I Study of Ex Vivo Expanded Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells for the Treatment of Pediatric Perianal Fistulizing Crohn's Disease.

机构信息

Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, OH, USA.

National Center for Regenerative Medicine, Cleveland, OH, USA.

出版信息

Inflamm Bowel Dis. 2023 Dec 5;29(12):1912-1919. doi: 10.1093/ibd/izad100.

DOI:10.1093/ibd/izad100

PMID:37263018

Abstract

BACKGROUND

Perianal fistulizing Crohn's disease is notoriously difficult to treat. Recent studies of mesenchymal stem cells have demonstrated safety and efficacy of this novel treatment approach. However, no studies to date have included pediatric patients. We sought to determine safety and efficacy of mesenchymal stem cells for pediatric perianal fistulizing Crohn's disease.

METHODS

This was a phase I clinical trial to evaluate safety and feasibility of mesenchymal stem cells in pediatric perianal Crohn's patients 13 to 17 years of age. At the time of an exam under anesthesia, following curettage of the fistula tract and closure of the internal opening with absorbable suture, 75 million mesenchymal stem cells were administered with a 22-gauge needle. This was repeated at 3 months if complete clinical and radiographic healing were not achieved. Adverse and serious adverse events at were measured at postprocedure day 1, week 2, week 6, month 3, month 6, and month 12. Clinical healing, radiographic healing per magnetic resonance imaging, and patient-reported outcomes were measured at the same time points.

RESULTS

Seven pediatric patients were enrolled and treated (6 male; median age of 16.7 years). There were no adverse or serious adverse events related to the investigational product or injection procedure. At 6 months, 83% had complete clinical and radiographic healing. The perianal Crohn's Disease Activity Index, Wexner incontinence score, and Van Assche score had all decreased at 6 months.

CONCLUSIONS

Bone marrow-derived mesenchymal stem cells offer a safe, and likely effective, treatment approach for pediatric perianal fistulizing Crohn's disease.

摘要

背景

肛周瘘管型克罗恩病的治疗极具挑战性。最近的间充质干细胞研究表明，这种新型治疗方法具有安全性和有效性。然而，迄今为止尚无研究纳入儿科患者。我们旨在确定间充质干细胞治疗儿童肛周瘘管型克罗恩病的安全性和疗效。

方法

这是一项 I 期临床试验，旨在评估间充质干细胞治疗 13 至 17 岁肛周克罗恩病儿童患者的安全性和可行性。在全身麻醉下进行检查时，在刮除瘘管和用可吸收缝线闭合内口后，用 22 号针头注射 7500 万间充质干细胞。如果未达到完全临床和放射影像学愈合，则在 3 个月时重复注射。在术后第 1 天、第 2 周、第 6 周、第 3 个月、第 6 个月和第 12 个月测量不良事件和严重不良事件。在相同时间点测量临床愈合、磁共振成像的放射影像学愈合和患者报告的结果。