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.
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