Efeitos do transplante autólogo de células-tronco mesenquimais em pacientes com Doença de Crohn refratária associada a fístulas perianais

Abstract

Introduction: Crohn's disease (CD) is an inflammatory bowel disease, which is characterized by inflammation of the mucosa and perianal complications, such as fistulas, which can affect about one third of patients. Despite the existence of therapies to improve symptoms, some individuals do not respond to conventional medical treatments, requiring alternative therapies. In this context, cell therapy, through transplantation of mesenchymal stem cells (MSC) is promising for the control of the inflammatory process of perianal fistulas in refractory CD. Objective: We evaluated the efficacy and safety of autologous transplantation of adipose tissue-derived MSC in patients with refractory perianal fistulizing CD. Methods: Six adult patients were recruited, with a proven diagnosis of refractory perianal fistulizing CD, and the proposed intervention was three applications of MSC (1.6 x 106 cells / mL in each application). The cells were isolated from the adipose tissue, from the flanks, by liposuction and cultured with Dulbecco´s Modified Eagle´s Medium, fetal bovine serum and antibiotic / antimycotic. Before applications, the parameters of morphology, absence of contamination, viability, ability to adhere to the plastic surface, immunophenotyping and differentiation potential of the cells were analyzed. The evaluation of transplants occurred in the 12th and 24th weeks after the first application, considering aspects of safety and efficacy, which were compared to the data at the beginning of the intervention. Results: Three patients completed the study and MSC were inoculated in passages 4, 5 and 6 in eight fistulas in total. In four fistulas, the external opening was closed, with local re-epithelialization, two of which closed in the 12th week. However, in the 24th week, the pelvic MRI exam indicated improvement in only one of the patients. On the other hand, in the same period, the clinical index of activity of the perianal disease and the evaluation of the quality of life indicated progress for the three patients and, through the analysis of the simple endoscopic score of CD, two patients presented the endoscopically inactive disease to the end of follow-up. As for anthropometric measurements, most were shown to be adequate and the foods that had low consumption throughout the study, in accordance for the three evaluated, were those that belong to the group of beans. Conclusion: Autologous MSCs from adipose tissue have clinical potential to safely and safely treat perianal fistulas in refractory CD.