MSC Intratissular Injection in Crohn Disease Patients

Inclusion Criteria: * Patients ≥ 18 years of age * Signing the informed consent * Diagnosis of Crohn Disease for more than 6 months * Presence of at least one Crohn Disease lesion refractory to conventional therapies (azathioprine, 6-mercaptopurine or methotrexate) and to biologic treatments (anti-Tumor Necrosis Factor therapies, vedolizumab, or ustekinumab). * Refractory lesion defined by (1) a stricture with a length of 2 to 5cm of the colon or the ileum accessible by ileocolonoscopy (i.e. a lesion identified during a colonoscopy with a lumen narrowing non passable by the colonoscope), (2) unhealed deep ulcer of the colon or the ileum accessible to ileocolonoscopy, or (3) actively draining perianal fistula(s). * Twenty patients with stricture(s), 20 patients with unhealed deep ulcer(s), and 20 patients with an actively draining perianal fistula(s) will be included Exclusion Criteria: * Indication for immediate luminal surgery * Intestinal obstruction * Intra-abdominal fistulas or abscess * Intestinal/colonic stricture or deep unhealed ulcer not accessible to ileocolonoscopy * Undrained peri-anal abscess * Pregnant women or planning pregnancy within one year * Positive stool culture/toxin for clostridium difficile pathogen or other pathogens * Renal failure (anuria, serious fluid overload, Glomerular Filtration Rate \< 30 ml/min, dialysis) or hepatic failure (Fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \>3 mg/dL) * documented human immunodeficiency virus infection; active hepatitis B, C, or tuberculosis * an opportunistic infection within 6 months before screening or a serious infection in the previous 3 months * malignancy within the past 5 years; or a history of lymphoproliferative disease