Safety and Efficacy of Autologous and Metabolically Fit Bone Marrow Mesenchymal Stromal Cells (Bm-Msc) in Medically Refractory Crohn'S Disease (Cd)

CD is a chronic auto-inflammatory disorder with devastating consequences including need for multiple intestinal resections. The most effective therapy, anti-TNF biologics, poses risks for serious infections and malignancies demands alternative approaches including MSCs. Thawed BM-MSCs deploy a heat shock response and impaired immune suppression in vitro. We hypothesized metabolically fit “fresh” autologous MSCs may improve their clinical potency, hence we performed FDA approved Phase I dose escalation clinical trial in 12 human subjects with CD (NCT01659762). The primary end point was safety and tolerability while efficacy was secondary endpoints. Ages (18–52) with a CD Activity Index (CDAI) of >220 were enrolled. Screening included normal pulmonary and renal function tests, CXR and negative TB, CMV tests. Autologous MSCs were isolated from iliac bone marrow aspirate and propagated for 2–3 weeks with fibrinogen depleted human platelet lysate. 12 subjects (n = 4 in each group) received a single MSC intravenous infusion of either 2x10^6 cells/kg, 5x10^6 cells/kg, or 10x10^6 cells/kg. Cells were infused over one hour with monitoring. MSCs were analyzed for cell surface marker by FACS to confirm identity, their ability to upregulate expression of IDO by IFNγ stimulation and inhibition of third party PBMC proliferation in vitro.