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

Abstract

Background Complex cryptoglandular perianal fistula (CPAF) is a kind of anal fistula that may cause anal incontinence after surgery. Minimally invasive surgery of anal fistula is constantly emerging. Over the past 20 years, there are several sphincter-sparing surgeries, one of which is autologous adipose-derived stem cell (ADSC) transplantation. However, to date, there is no study regarding the treatment of complex CPAF with ADSC in China. This is the first study in China on the treatment of complex CPAF with ADSC to evaluate its safety and efficacy. Methods Totally, 24 patients with complex CPAF were enrolled in this prospective case-control study from January 2018 to December 2019 in the National Colorectal Disease Center of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Patients were divided into ADSC group and endorectal advancement flap (ERAF) group according to their desire. The healing of fistulas (healing of all treated fistulas at baseline, confirmed by doctor’s clinical assessment and magnetic resonance imaging or transrectal ultrasonography) was evaluated at week 12 after treatment. In addition to their safety evaluation based on adverse events monitored at each follow-up, the patients were also asked to complete some scoring scales at each follow-up including pain score with visual analog score (VAS) and anal incontinence score with Wexner score. Results The closure rates within ADSC group and ERAF group at week 12 were 54.55% (6/11) and 53.85% (7/13), respectively, without significant difference between them. VAS score in ADSC group was significantly lower than that in ERAF group at the 5th day postoperatively [1(0,2) VS 2(2,4), p = 0.011], but no differences were observed at the other time. Wexner score of all patients was not increased with no significant differences between the two groups. Adverse events were observed fewer in ADSC group (27.27%) than that in ERAF group (53.85%), but there was no significant difference between them. Conclusion This study indicated safety and efficiency of ADSC for the treatment of complex CPAF in the short term, which is not inferior to that of ERAF. ADSC may provide a promised and potential treatment for complex CPAF conforming to the future of the treatment, which is reconstruction and regeneration. Trail registration ChiCTR, ChiCTR1800014599. Registered 23 January 2018—retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=24548

Mesenchymal Stem Cells for Cryptoglandular Anal Fistula: Current State of Art

“…The description of healing is clinical, with some differences when Magnetic Resonance is used. In some trial we observed a success in more than of 70% of patients ( 22 , 24 , 27 ), but with fewer patients this rate of healing suddenly decreases ( 28 , 29 ), also for the learning curve. Complications are frequent, even if major adverse events are rare and with an easy resolution: most common are perianal abscess especially at the beginning of the experience ( 27 ).…”

“…Recently, the use of ASCs was compared not only with fibrin glue but also with other surgical techniques, such as endorectal (29). A phase I trial shows an association with a different technique for the closure of fistula tracts, the anal plug: 15 patients with trans-sphincteric cryptoglandular fistulas received a MSC-loaded fistula plug, with complete healing reported in three and "partial" in 7 (28).…”

Advanced Regenerative Medicine Strategies for Treatment of Perianal Fistula in Crohn’s Disease

“…67 Data from clinical trial studies for the treatment of fistula using ASCs are reported in Table 1. [75][76][77][78][80][81][82][83][84][85][86][87][88]…”

Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas

“…Local injection of adipose tissue-derived mesenchymal stem cells (AT-MSCs) has emerged as a novel approach with promising outcome in the treatment of both cryptoglandular fistulas and fistulizing Crohn’s disease [ 8 , 9 ]. A variety of approaches have been reported including the use of cultured autologous stem cells [ 10 ] or in vitro expanded allogenic AT-MSCs that showed in a large phase 3 clinical trial, 50% in intervention compared to 30% healing rate of anal fistulas in patients with Crohn’s disease in the control group at 24 weeks follow up [ 11 ].…”

“…A variety of approaches have been reported including the use of cultured autologous stem cells [ 10 ] or in vitro expanded allogenic AT-MSCs that showed in a large phase 3 clinical trial, 50% in intervention compared to 30% healing rate of anal fistulas in patients with Crohn’s disease in the control group at 24 weeks follow up [ 11 ]. Other clinical studies reported a positive effect of using autologous AT-MSCs on a closure rate (around 50%) in the patients with cryptoglandular perianal fistulas in short and long term follow up period using different techniques and concentration of stem cells [ 9 , 12 ]. However, these cell products require laboratory facilities to isolate and expand the cells in vitro and manufacturing the product is time consuming and very expensive.…”