P086. Donor dependent efficacy of human mesenchymal stromal cell treatment in experimental colitis
I. Molendijk1, V.L. van Zuijlen2, H.W. Verspaget1, W.E. Fibbe2, H. Roelofs2, D.W. Hommes3, 1Leiden University Medical Center, Gastroenterology and Hepatology, Leiden, Netherlands, 2Leiden University Medical Center, Immunohematology and Blood Transfusion, Netherlands, 3University of California Los Angeles, Digestive Diseases, Los Angeles, United States
Mesenchymal stromal cells (MSCs) are multipotent cells capable of differentiating into multiple cell lineages of the mesenchyme. They have both potent immunosuppressive and tissue regenerative effects. In experimental colitis models, MSCs have shown positive effects on clinical endpoints. MSCs are also being explored in clinical trials as therapy for Crohn's Disease.
We compared the efficacy of human bone marrow-derived MSCs (hBM-MSC) in mild and severe experimental colitis and focused on potential MSC donor effects. MSCs were expanded from three BM aspirates from healthy human donors. Single or multiple MSC infusions (0.5×106 MSCs) were administered and 6 hours after the first MSC infusion DSS was administered in the drinking water of C57BL/6 mice for 7 days. Body weight was monitored for 10 days and subsequently mice were sacrificed for analyses, including disease and histology scores and inflammatory cytokine profile. The hBM-MSC populations were characterized by flow cytometry, differentiation capacity and their inhibitory effect on T cell proliferation in a PBMC proliferation inhibition assay.
Mild and severe colitis was induced using 1.25% and 1.75% DSS resulting in a reduction of initial body weight of 5% and 15%, respectively. Depending on the hBM-MSC donor used, in both the mild and the severe colitis group, a significant amelioration of the induced colitis and an earlier recovery in body weight (p < 0.05) compared to PBS controls was seen upon a single MSC infusion. In vitro characterization of the different MSC populations used did not reveal any phenotypic or functional differences, as reflected by identical expression of CD73, CD90 and CD105 and MLR inhibitory activity. Remarkably, multiple injections of MSCs during the colitis induction was found not to affect the severity of the colitis. Whether histology scores and cytokine profiles also reflect MSC donor-dependent differences is currently under investigation.
We established a DSS model for mild and for severe experimental colitis. A single, but not multiple, hBM-MSC infusion was found to have a positive clinical effect on colitis induction and recovery as assessed by body weight recovery, both in the mild and the severe colitis group. However, this clinical effect was found to be donor-related. These observations may have an impact on the clinical use of MSC treatment in colitis.