dose escalation of allogeneic adipose derived stroma/stem cells for the treatment of crohn's fistula

Conditions: Crohn Disease

Summary: perianal fistulas are in the forefront (42 to 72, 4%) of morbid complication of crohn's disease, affecting nearly one- third of patients and complicating abscesses in 35-48% of cases. the current treatment is based on the combination of drainage (proctologic and surgical), and biologics techniques, but the failure rate varies from 30 to 80%. actually, innovative cell therapy procedures are validated by cell-easy with the use of allogenic mesenchymal stem cells for the immunomodulatory, anti-inflammatory, angiogenic and trophic properties (cellready®) and represent a promising option in the treatment of perianal fistulas associated with crohn's disease. this phase i/ii study is designed to evaluate the treatment of complex perianal fistulas associated with crohn's disease, after failure of conventional treatment by injection of allogeneic cultured adipose-derived stromal cell (admsc) into the fistula.

the injection of adipose stromal cells is currently evaluated in clinical studies for repair-damaged tissues in various diseases (limb ischemia, osteoarthritis, systemic slerosis...). immunoregulatory and anti-inflammatory properties of admsc's are responsible for accelerating healing and represents an innovative approach to treat perianal fistulas associated with crohn's disease. this phase i/ii study is designed to evaluate the treatment of complex perianal fistulas associated with crohn's disease, after failure of conventional treatment by injection of admsc (cellready®) into the fistula. different doses of admsc will be tested for a dose escalation (5.10\*7 and 10.10\*7 cells) and injected in the in the wall of the fistula.

Eligibility criteria:
inclusion criteria: * patients over 18 years old, * patients who signed the informed consent, * patient affiliated to a social security system, * controlled luminal crohn's disease characterized by an harvey-bradshaw score less or equal than 8 and diagnosed on clinical, endoscopic, histological and/or radiological criteria for more than 3 months, * colonoscopy less than a year old without ulcer in the rectum, * presence of complex chronic perianal fistula with a maximum of two internal ports and three external ports, * patient treated with a combined treatment (drainage on setons + anti-tnfα) and who failed conventional treatment after 6 months and whose intraluminal disease (intestinal damage) is controlled exclusion criteria: * refusal of the patient to participate in the study, * positive quantiferon test, * patient with transplanted organ, * history of cancer in the last five years or lympho-proliferative disease, * persistent bacterial or viral infection, * patient with a contraindication to mri, * known allergy to gadolinium, * known allergy to albumine, * end-stage organ failure, * pregnant or breastfeeding women, * women of childbearing age without effective contraception throughout the duration of the study, * patient under judicial protection, under guardianship or curatorship. * patient previously treated with alofisel®

Keywords: crohn's disease perianal fistula regenerative medicine immunomodulation allogeneic adipose-derived stem cell