García-Olmo Damián, García-Arranz Mariano, Herreros Dolores, Pascual Isabel, Peiro Concepción, Rodríguez-Montes José Antonio
Department of General Surgery, La Paz University Hospital, Madrid, Spain.
Dis Colon Rectum. 2005 Jul;48(7):1416-23. doi: 10.1007/s10350-005-0052-6.
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 healing of Crohn's fistulas.
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.
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).
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.
对克罗恩病患者的瘘管进行有效管理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分化为多种细胞类型。因此，我们尝试使用这类细胞来促进克罗恩病瘘管的愈合。
我们设计了一项前瞻性I期临床试验，纳入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。我们还研究了用于移植的脂肪抽吸物来源细胞的各种细胞标志物表达及生长速率。
1例患者因培养细胞被细菌污染而被排除。我们用第3代或更早代次的自体脂肪组织来源干细胞对4例患者的9个瘘管进行了接种。8个接种的瘘管每周随访至少8周。在6个瘘管中，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2个瘘管中，外部开口仅不完全闭合，流出量减少（未愈合；25%）。随访期结束时，未在任何患者中观察到不良反应（最短随访12个月；最长随访30个月；平均随访22个月）。
据我们所知，这是首次关于使用从脂肪抽吸物中获得的自体干细胞进行细胞治疗的临床试验报告。我们的结果表明，我们的方案用于治疗克罗恩病瘘管是可行且安全的。纳入的患者数量以及I期临床试验的非对照性质不允许证明该治疗的有效性。然而，本研究结果鼓励开展进一步的II期研究。
