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Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn's disease: results of a phase I study
  1. Marjolijn Duijvestein1,
  2. Anne Christine W Vos1,
  3. Helene Roelofs2,
  4. Manon E Wildenberg1,
  5. Barbara B Wendrich1,
  6. Henricus W Verspaget1,
  7. Engelina M C Kooy-Winkelaar2,
  8. Frits Koning2,
  9. Jaap Jan Zwaginga2,
  10. Herma H Fidder1,
  11. Auke P Verhaar1,
  12. Willem E Fibbe2,
  13. Gijs R van den Brink1,
  14. Daniel W Hommes1
  1. 1Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr M Duijvestein, Department of Gastroenterology and Hepatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands; m.duijvestein{at}lumc.nl

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 1–2×106 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.

  • Crohn's Disease
  • mesenchymal stem Cell
  • mesenchymal stromal Cell
  • MSC
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Footnotes

  • Funding This work was supported by grants from the Dutch Digestive Diseases Foundation (MLDS, W07-17), Digest Science Grant and a grant from ZonMW (TAS).

  • Competing interests None declared.

  • Ethics approval This study was conducted with the approval of the Medical Ethical Committee of the Leiden University Medical Center (LUMC) and the Central Committee on Research involving Human Subjects (CCMO, The Hague, The Netherlands). http://www.trialregister.nl/ identifier: NTR1360.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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