Our objective is to apply autologous bone marrow-derived Mesenchymal Stem Cells (MSCs) for refractory Crohn’s disease; then, determine immunomodulatory effects of MSCs into TH1 and TH17 immune responses, and in the treatment of refractory Crohn’s disease patients.
Seventeen adult patients with refractory Crohn’s disease will be entered to the study. Criteria for patient inclusion is that patients at least 18 years of age and have moderate to severe Crohn’s disease, as define by a baseline Crohn’s Disease Activity Index (CDAI) score between 220 and 450. Furthermore, patients have to be refractory to the standard treatment options for Crohn’s disease. We define refractory patients as patients that, at some time during the course of the disease, must have received steroids, immunosuppressive agents (eg, azathioprine, 6-mercaptopurine or methotrexate) or anti-TNF therapy which did not result in an adequate response to treatment. Colonoscopy will be performed at baseline to confirm disease activity. All patients will be taken informed consent. Patients will be underwent bone marrow aspiration under local anesthesia, and Bone marrow MSCs will be isolated and will be expanded ex vivo. Two intravenous infusions of 0.5 to 2 ×106 cell/kg a week apart will be used. Gene expression as well as serum levels of TGFβ, IL-17A, IL-10, IL-4,IL-23,and IFN-γ Cytokines will be determined by RT-PCR and ELISA, respectively. Also, TH1, TH17, and Treg Subpopulations will be measured by flowcytometry.