A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation
A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation
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DOI：
10.1007/s10350-005-0052-6
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发表时间：
2005-07-01
影响因子：
3.9
通讯作者：
Rodríguez-Montes, JA
中科院分区：
文献类型：
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作者：
García-Olmo, D;García-Arranz, M;Rodríguez-Montes, JA
目的：克罗恩病患者瘘管的有效治疗是一个极具挑战性的问题。从某些组织如脂肪组织中提取的间充质成体干细胞可以分化成各种细胞类型。因此，我们尝试使用这样的细胞来刺激克罗恩氏瘘管的加热。方法：我们设计了一项前瞻性I期临床试验，涉及5例克罗恩病患者，以测试自体干细胞移植治疗瘘管的可行性和安全性。我们还研究了各种细胞标记物的表达和用于移植的脂肪抽吸物衍生细胞的生长速率。结果：1例患者因培养细胞细菌污染而被排除。我们在4例患者的9个瘘管中接种了第3代或更早的自体脂肪组织来源的干细胞。8例接种瘘管每周随访至少8周。在6例瘘管中，在第8周结束时，外部开口被上皮覆盖，因此，这些瘘管被认为已愈合（75%）。在另外两个瘘管中，只有外部开口不完全闭合，输出流量减少（未愈合; 25%）。在随访期结束时（最短随访时间，12个月;最长随访时间，30个月;平均随访时间，22个月），在任何患者中均未观察到不良反应。结论：据我们所知，这是第一个报告的临床试验的细胞治疗使用自体干细胞从脂肪抽吸。我们的研究结果表明，我们的协议是可行的，安全的治疗克罗恩病瘘。纳入的患者数量和I期临床试验的非对照性质不允许证明治疗的有效性。然而，本研究的结果鼓励在第二阶段进行进一步的研究。
PURPOSE: The effective management of fistulas in patients with Crohn's disease presents an extremely challenging problem. Mesenchymal adult stem cells extracted from certain tissues, such as adipose tissue, can differentiate into various cell types. Therefore, we have tried to use such cells to stimulate heating of Crohn's fistulas. METHODS: We designed a prospective Phase I clinical trial, involving five patients with Crohn's disease, to test the feasibility and safety of autologous stem cells transplantation in the treatment of fistulas. We also studied the expression of various cell markers and the growth rates of the lipoaspirate-derived cells that were used for transplantation. RESULTS: One patient was excluded because of bacterial contamination of cultured cells. We inoculated nine fistulas in four patients with autologous adipose tissue-derived stem cells at Passage 3 or earlier. Eight inoculated fistulas were followed weekly for at least eight weeks. In six fistulas, the external opening was covered with epithelium at the end of Week 8, and, thus, these fistulas were considered healed (75 percent). In the other two fistulas, there was only incomplete closure of the external opening, with a decrease in output flow (not healed; 25 percent). No adverse effects were observed in any patient at the end of the follow-up period (minimum follow-up, 12 months; maximum follow-up, 30 months; follow-up average, 22 months). CONCLUSIONS: To our knowledge, this is the first report of a clinical trial of cell therapy using autologous stem cells obtained from a lipoaspirate. Our results indicate that our protocol is feasible and safe for the treatment of fistulas in Crohn's disease. The number of patients included and the uncontrolled nature of Phase I clinical trials do not allow demonstration of the effectiveness of the treatment. However, the results of the present study encourage to perform further studies in Phase II.