LAUSR

BACKGROUND Due to their immunoregulatory and tissue regenerative features, mesenchymal stromal cells (MSCs) are a promising novel tool for the management of ulcerative proctitis (UP). Here we report on a phase IIa clinical study to evaluate the impact of local MSC therapy in UP. METHODS Thirteen refractory UP patients, with endoscopic Mayo score (EMS) 2 or 3, were included. Seven patients received 20-40 x 106 allogeneic MSCs (cohort 1), while six patients received 40-80 x 106 MSCs (cohort 2). Adverse events (AEs) were assessed at baseline and week 2, 6, 12, and 24. Clinical, endoscopic, and biochemical parameters were assessed at baseline, week 2 and 6. Furthermore, we evaluated the engraftment of MSCs, presence of donor-specific human leukocyte antigen (HLA) antibodies (DSAs), and we determined the impact of MSC therapy on the local immune compartment. RESULTS No serious AEs were observed. The clinical Mayo score was significantly improved at week 2 and 6, and the EMS was significantly improved at week 6, compared to baseline. At week 6, donor MSCs were still detectable in rectum biopsies of 4/9 patients and DSAs against both HLA-class I and -class II were found. Mass cytometry showed a reduction of activated CD8+ T cells and CD16+ monocytes and an enrichment in mononuclear phagocytes and natural killer cells in biopsies after local MSC therapy. CONCLUSION Local administration of allogeneic MSCs is safe, tolerable, and feasible for treatment of refractory UP and shows encouraging signs of clinical efficacy and modulation of local immune responses. This sets the stage for larger clinical trials. TRIAL REGISTRATION clinicaltrialsregister.eu, EudraCT: 2017-003524-75, Dutch Trial register: NTR7205. FUNDING ECCO grant 2020.