ABSTRACT
Perianal fistulas in Crohn's disease are frequent and disabling, with a major impact on patients' quality of life. Cell-based therapy using mesenchymal stem cells represents new hope for these patients, but long-term efficacy remains challenging. In a pilot study, including patients with refractory complex perianal fistulas, autologous adipose-derived stromal vascular fraction (ADSVF) combined with microfat achieved combined remission in 60% of cases, with a good safety profile at 1 year. The purpose of this study is to assess whether these results were maintained at longer term. The safety and efficacy data of the ten patients were evaluated retrospectively 3 years after injection on the basis of clinical and radiological data. MRI were analysed according to the MAGNIFI-CD score. No adverse event was attributed to the experimental stem-cell treatment. Combined remission was achieved in 7 patients (70%) and associated with a significant improvement in the MAGNIFI-CD MRI score. In conclusion, the safety and efficacy of ADSVF and microfat injection in Crohn's disease fistulas were maintained at 3 years, demonstrating that this innovative strategy is effective in producing a long-lasting healing effect. The ongoing multicentre randomized placebo-controlled trial (NCT04010526) will be helpful to define the place for this approach in the current therapeutic arsenal.
Subject(s)
Crohn Disease , Mesenchymal Stem Cell Transplantation , Rectal Fistula , Crohn Disease/complications , Crohn Disease/therapy , Humans , Mesenchymal Stem Cell Transplantation/methods , Pilot Projects , Quality of Life , Rectal Fistula/etiology , Rectal Fistula/therapy , Retrospective Studies , Stromal Vascular Fraction , Treatment OutcomeSubject(s)
Adipose Tissue/transplantation , Cell Transplantation/methods , Mesenchymal Stem Cells , Microinjections/methods , Rectal Fistula/etiology , Rectal Fistula/surgery , Adipocytes/transplantation , Adult , Crohn Disease/complications , Crohn Disease/diagnosis , Crohn Disease/therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Safety , Prospective Studies , Rectal Fistula/diagnostic imaging , Recurrence , Risk Assessment , Time Factors , Treatment Outcome , Young AdultABSTRACT
Mesenchymal stem cell therapy is a promising treatment for perianal Crohn's fistulas refractory to conventional therapy, which are an extremely morbid complication and a true therapeutic challenge. Autologous adipose-derived stromal vascular fraction (ADSVF) is an easily accessible source of cells with angiogenic, anti-inflammatory, immunomodulatory, and regenerative properties. Here, we describe a case involving a patient with severe perianal Crohn's fistulas refractory to the best medical and surgical practices who received local treatment with ADSVF and microfat. This patient was first examined under anesthesia with drainage via seton placement; 1 week later, on a single day, he underwent adipose tissue extraction, ADSVF and microfat preparation, and the local injection of 14 ml of microfat and approximately 20 million viable ADSVF cells into the soft tissue around the fistulas. No serious adverse events were observed. At the first endpoint at 12 weeks, the fistula had clinically healed with complete re-epithelialization of all external openings; no fistula tract was detected on magnetic resonance imaging, confirming this finding. This good clinical outcome was sustained at 48 weeks and was associated with a reduction in the severity of perianal disease and an improvement in quality of life. The current case highlights the therapeutic potential of a new cellular treatment for Crohn's patients with refractory perianal fistulas based on the innovative hypothesis that the combined action of ADSVF in association with the trophic characteristics of a microfat graft could be beneficial for this condition. TRIAL REGISTRATION: EudraCT number 201325, NCT02520843 . Registered on 5 August 2015.
