Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis

Mult Scler. 2018 Apr;24(4):501-511. doi: 10.1177/1352458517703802. Epub 2017 Apr 6.

Abstract

Background: Mesenchymal stem cells (MSCs) exhibit immunomodulatory, tissue-protective, and repair-promoting properties in vitro and in animals. Clinical trials in several human conditions support the safety and efficacy of MSC transplantation. Published experience in multiple sclerosis (MS) is modest.

Objective: To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS.

Methods: Participants with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS), Expanded Disability Status Scale score 3.0-6.5, disease activity or progression in the prior 2 years, and optic nerve involvement were enrolled. Bone-marrow-derived MSCs were culture-expanded and then cryopreserved. After confirming fulfillment of release criteria, 1-2 × 106 MSCs/kg were thawed and administered IV.

Results: In all, 24 of 26 screened patients were infused: 16 women and 8 men, 10 RRMS and 14 SPMS, mean age 46.5, mean Expanded Disability Status Scale score 5.2, 25% with gadolinium-enhancing magnetic resonance imaging (MRI) lesions. Mean cell dosage (requiring 1-3 passages) was 1.9 × 106 MSCs/kg (range, 1.5-2.0) with post-thaw viability uniformly ⩾95%. Cell infusion was tolerated well without treatment-related severe or serious adverse events, or evidence of disease activation.

Conclusion: Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.

Trial registration: ClinicalTrials.gov NCT00813969.

Keywords: Multiple sclerosis; clinical trial; disability measures; mesenchymal stem cells; quantitative MRI; safety.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Disease Progression
  • Female
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation* / methods
  • Mesenchymal Stem Cells / cytology*
  • Middle Aged
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis, Chronic Progressive / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Transplantation, Autologous / methods
  • Young Adult

Associated data

  • ClinicalTrials.gov/NCT00813969