Chapter six Autologous bone marrow derived mesenchymal stromal cell treatment for refractory luminal Crohn’s disease: results of a phase I study

Background and aim: Mesenchymal stromal cells (MSCs) are pluripotent cells that have immunosuppressive effects both in vitro and in experimental colitis. Promising results of MSC therapy have been obtained in patients with severe graft versus host disease of the gut. Our objective was to determine the safety and feasibility of autologous bone marrow derived MSC therapy in patients with refractory Crohn’s disease (CD). Patients and intervention: Ten adult patients with refractory CD (8 females/2 males) underwent bone marrow aspiration under local anesthesia. Bone marrow MSCs were isolated and expanded ex vivo. MSCs were tested for phenotype and functionality in vitro. Nine patients received 2 doses of 1-2x10^6 cells/kg bodyweight, intravenously, 7 days apart. During follow up, possible side effects and changes in patients’ Crohn’s disease activity index (CDAI) scores were monitored. Colonoscopies were performed at week 0 and 6, and mucosal inflammation was assessed by using the Crohn’s disease endoscopic index of severity (CDEIS). Results: MSC isolated from CD patients showed similar morphology, phenotype and growth potential compared to MSCs from healthy donors. Importantly, immunomodulatory capacity was intact, as CD MSCs significantly reduced peripheral blood mononuclear cell proliferation in vitro. MSC infusion was without side effects, besides a mild allergic reaction probably due to the cryopreservant DMSO in one patient. Baseline median CDAI was 326 (224-378). Three patients showed clinical response (CDAI decrease ≥70 from baseline) 6 weeks post treatment, conversely three patients required surgery due to disease worsening. Conclusions: Administration of autologous bone marrow derived MSCs appears safe and feasible in the treatment of refractory CD. No serious adverse events were detected during bone marrow harvesting and administration. 111 Autologous bone marrow derived mesenchymal stromal cell treatment for refractory luminal Crohn’s disease

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