The injection of adipose tissue-derived products is emerging as a new therapeutic option. Various Preclinical models have documented the superiority of ADSVF over purified stem cells for tissue repair, lying on the heterogeneity of ADSVF that gathers various cell types displaying synergistic regenerative properties [6]. In addition, the local injection of both ADSVF and microfat is expected to provide complementary effects: ADSVF supports strong regenerative effects while microfat allows a volumizing effects that facilitates closure of fistulas [8]. We reported here that local injection of ADSVF and microfat did not cause any adverse effects over a 3-year follow-up period, providing evidence of a good long-term safety profile. The adverse events observed were considered to be expected as Crohn's disease progresses.
Importantly, this procedure led to combined remission for 70% of patients at 3 years. This high rate of efficacy provides the first evidence of a long-lasting healing effect of the innovative procedure, as 83% of patients maintained the combined remission observed at 1 year. In addition, our results also indicate a possible delayed effect of SVF and microfat. Indeed, two patients achieved combined remission only at 3 years. This hypothesis is supported by the absence of change in pharmacological treatment or surgery of the treated fistula in one patient. However, for the other patient who had a substantial treatment change and received surgical drainage with setons, it is difficult to specifically attribute the positive outcome to the study procedure. Of note, the level of remission at 3 years was not associated with a significant improvement in the PDAI score, whereas it was at 1 year. Consistently, in the ADMIRE study, success of perianal fistulas healing with expanded allogeneic MSCs did not impact the PDAI score at 24 and 52 weeks follow-up [4, 5].
Although the promise of ADSVF-based therapy has been documented in various pathologies, long-term efficacy is rarely reported. We previously reported data in favour of the long-term safety and efficacy of ADSVF injection in the hands of patients with systemic sclerosis [11]. In the field of Crohn’s disease, long-term studies only concerned expanded MSC, mainly reported data from 1 year follow-up [12] or evaluated repeated cell-based therapy procedures. Ciccocioppo and colleagues reported a 4-year follow-up with a 37% probability of fistula relapse-free survival after multiple injections of bone marrow MSCs [13]. Guadalajara et al. also described a two-step injection procedure of ADSCs mixed with fibrin glue with 40% (2/5) of patients sustaining remission at 3 years [14]. A common point between these studies was the limited number of patients followed in the long term [13, 14].
In conclusion, we confirmed the safety profile of an innovative cell-based therapy approach combining ADSVF and autologous microfat injection in refractory complex perianal fistulas of Crohn's disease and provided efficacy data in long-term assessment. As it was a pilot protocol, our study was limited by its retrospective design, the small number of patients and the absence of a control group. Accordingly, a dedicated randomized placebo-controlled trial is currently conducted (NCT04010526) to assess the efficacy of ADSVF and microfat and define the place for this approach in the current therapeutic arsenal.