| Autor: |
Ouboter LF; Department of Gastroenterology and Hepatology.; Department of Immunology., Barnhoorn MC; Department of Gastroenterology and Hepatology., Verspaget HW; Department of Gastroenterology and Hepatology., Plug L; Department of Gastroenterology and Hepatology., Pool ES; Department of Hematology, and., Szuhai K; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands., Hawinkels LJ; Department of Gastroenterology and Hepatology., van Pel M; Department of Immunology.; Netherlands Center for the Clinical Advancement of Stem Cell & Gene Therapies (NECSTGEN), Leiden, Netherlands.; Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands., Zwaginga JJ; Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands., Roelen D; Department of Immunology., Koning F; Department of Immunology., Pascutti MF; Department of Immunology., van der Meulen-de Jong AE; Department of Gastroenterology and Hepatology. |
| Jazyk: |
angličtina |
| Zdroj: |
JCI insight [JCI Insight] 2023 May 08; Vol. 8 (9). Date of Electronic Publication: 2023 May 08. |
| DOI: |
10.1172/jci.insight.167402 |
| Abstrakt: |
BACKGROUNDDue 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 that evaluated the impact of local MSC therapy on UP.METHODSThirteen refractory UP patients, with an endoscopic Mayo score (EMS) of 2 or 3, were included. Seven patients received 20-40 million allogeneic MSCs (cohort 1), while 6 patients received 40-80 million MSCs (cohort 2). Adverse events (AEs) were assessed at baseline and on weeks 2, 6, 12, and 24. Clinical, endoscopic, and biochemical parameters were assessed at baseline and on weeks 2 and 6. Furthermore, we evaluated the engraftment of MSCs, the presence of donor-specific human leukocyte antigen (HLA) antibodies (DSAs), and we determined the impact of MSC therapy on the local immune compartment.RESULTSNo serious AEs were observed. The clinical Mayo score was significantly improved on weeks 2 and 6, and the EMS was significantly improved on week 6, compared with baseline. On week 6, donor MSCs were still detectable in rectal biopsies from 4 of 9 patients and DSAs against both HLA class I and class II were found. Mass cytometry showed a reduction in activated CD8+ T cells and CD16+ monocytes and an enrichment in mononuclear phagocytes and natural killer cells in biopsies after local MSC therapy.CONCLUSIONLocal 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 REGISTRATIONEU Clinical Trials Register (EudraCT, 2017-003524-75) and the Dutch Trial Register (NTR7205).FUNDINGECCO grant 2020. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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