Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up

Abstract

The aim of this clinical trial (ID Number NCT01803347) was to determine the safety and efficacy of autologous adipose‐derived stem cells (ASCs) for treatment of cryptoglandular fistula. This research was conducted following an analysis of the mistakes of a same previous phase III clinical trial. We designed a multicenter, randomized, single‐blind clinical trial, recruiting 57 patients. Forty‐four patients were categorized as belonging to the intent‐to‐treat group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue (group A) and 21 received intralesional fibrin glue (group B), both after a deeper curettage of tracks and closure of internal openings. Fistula healing was defined as complete re‐epithelialization of external openings. Those patients in whom the fistula had not healed after 16 weeks were eligible for retreatment. Patients were evaluated at 1, 4, 16, 36, and 52 weeks and 2 years after treatment. Results were assessed by an evaluator blinded to the type of treatment. After 16 weeks, the healing rate was 30.4% in group A and 42.8% in group B, rising to 55.0% and 63.1%, respectively, at 52 weeks. At the end of the study (2 years after treatment), the healing rate remained at 50.0% in group A and had reduced to 26.3% in group B. The safety of the cellular treatment was confirmed and no impact on fecal continence was detected. The main conclusion was that autologous ASCs for the treatment of cryptoglandular perianal fistula is safe and can favor long‐term and sustained fistula healing.

Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: a prospective case-control study

“…Our study indicated that the closure rate of ADSC was not inferior to that of ERAF at week 12 (54.55% VS 53.85%, p = 1.000). And it was similar to some other studies [ 15 , 19 ]. As Cho et al [ 32 ] and Choi et al [ 17 ] reported, we also thought that some failure of the cases with ADSC in this study may be caused by poor control of infection.…”

“…We still believed that ADSC has an advantage in pain relief. On the other hand, there was no incontinence due to the injury of sphincter in the study as previously literatures reported (Table 1 ) [ 14 – 19 ]. The damage of anal function after the operation of ERAF may be related to the stretch injuries to the muscle and nerve fibers caused by significant retraction and manipulation of the anus [ 33 ].…”

“…The study of fistula-in-ano’s treatment with mesenchymal stem cells (MSCs) had become a research hotspot, which had a great prospect and potential future application since Garcia-Olmo et al [ 26 ] And the American Food and Drug Administration and European Union approved CX601 (human allogeneic ADSC) for the treatment of Crohn’s fistula-in-ano in 2017 and 2018 respectively. Therefore, we believed that ADSC has a potential future application in the treatment of CPAF according to several previously published literatures (Table 1 ) [ 14 – 19 ].…”

“…1 ) [ 11 – 13 ]. Recently, ADSC, a new biotechnology, has also been reported as a safe and effective treatment of complex cryptoglandular perianal fistula (CPAF) in several previously published literatures (Table 1 ) [ 14 – 19 ]. We previously reported the experience of ADSC in the treatment of Crohn’s fistula-in-ano and concluded that it has the following advantages: protecting anal function of patients, relieving pain, allowing a quick recovery, being well-tolerated, and improving the quality of life during postoperative period [ 20 ].…”

HPV+ve/−ve oral-tongue cancer stem cells: A potential target for relapse-free therapy

“…The CSC niches allow the cell to remain dormant for a long time before initiating recurrent/distance metastasis [170] . Therefore, targeting whole tumor will not produce good results while targeting CSCs [171] . Furthermore, the cancer stem cells derived-exosomes are also crucial for tumor relapse, metastasis and maintenance.…”