Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn's disease: results of a phase I study
Abstract
Background and aim: Mesenchymal stromal cells (MSCs) are pluripotent cells that have immunosuppressive effects both in vitro and in experimental colitis. Promising results of MSC therapy have been obtained in patients with severe graft versus host disease of the gut. Our objective was to determine the safety and feasibility of autologous bone marrow derived MSC therapy in patients with refractory Crohn's disease. Patients and intervention: 10 adult patients with refractory Crohn's disease (eight females and two males) underwent bone marrow aspiration under local anaesthesia. Bone marrow MSCs were isolated and expanded ex vivo. MSCs were tested for phenotype and functionality in vitro. 9 patients received two doses of 1–2×10 6 cells/kg body weight, intravenously, 7 days apart. During follow-up, possible side effects and changes in patients' Crohn's disease activity index (CDAI) scores were monitored. Colonoscopies were performed at weeks 0 and 6, and mucosal inflammation was assessed by using the Crohn's disease endoscopic index of severity. Results: MSCs isolated from patients with Crohn's disease showed similar morphology, phenotype and growth potential compared to MSCs from healthy donors. Importantly, immunomodulatory capacity was intact, as Crohn's disease MSCs significantly reduced peripheral blood mononuclear cell proliferation in vitro. MSC infusion was without side effects, besides a mild allergic reaction probably due to the cryopreservant DMSO in one patient. Baseline median CDAI was 326 (224–378). Three patients showed clinical response (CDAI decrease ≥70 from baseline) 6 weeks post-treatment; conversely three patients required surgery due to disease worsening. Conclusions: Administration of autologous bone marrow derived MSCs appears safe and feasible in the treatment of refractory Crohn's disease. No serious adverse events were detected during bone marrow harvesting and administration.
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Clinical applications involving systemic administration of MSCs require a large number of cells (1-10 × 106 cells/kg) to demonstrate therapeutic efficacy.
“Clinical applications involving systemic administration of MSCs require a large number of cells (1–10 × 106 cells/kg) to demonstrate a therapeutic efficacy [27–29].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [29]
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- Authors
- Duijvestein, M., Vos, A. C. W., Roelofs, H., Wildenberg, M. E., Wendrich, B. B., Verspaget, H. W., Kooy-Winkelaar, E. M. C., Koning, F., Zwaginga, J. J., Fidder, H. H., Verhaar, A. P., Fibbe, W. E., van den Brink, G. R., & Hommes, D. W.
- Affiliations
- Leiden University Medical Center (NL)
- Corresponding author
- Duijvestein, Marjolijn
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2010-10-04
- Volume
- 59
- Issue
- 12
- Pages
- 1662-1669
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2105734762
- Cited by
- 622
- References
- 27
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 17 · 2023: 22 · 2022: 21 · 2021: 33 · 2020: 40 · 2019: 41 · 2018: 40 · 2017: 35 · 2016: 67 · 2015: 65 · 2014: 54 · 2013: 78 · 2012: 55
- FWCI
- 24.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Funders
- Leids Universitair Medisch Centrum
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- mesenchymal stem cells, bone marrow-derived stem cells, refractory Crohn's disease, autologous cell therapy, immunomodulation, peripheral blood mononuclear cell proliferation, CDAI, feasibility and safety, mucosal inflammation
- MeSH terms
- Adult, Cell Differentiation, Cells, Cultured, Colonoscopy, Crohn Disease, Dose-Response Relationship, Immunologic, Epidemiologic Methods, Female, Humans, Immune Tolerance, Male, T-Lymphocyte Subsets, Cytokines, Stromal Cells, Immunity, Mucosal, Mesenchymal Stem Cell Transplantation, Cell Proliferation, Young Adult
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