Clinical Outcomes of Transplanted Modified Bone Marrow-Derived Mesenchymal Stem Cells in Stroke: A Phase 1/2a Study

Stroke. 2016 Jul;47(7):1817-24. doi: 10.1161/STROKEAHA.116.012995. Epub 2016 Jun 2.

Abstract

Background and purpose: Preclinical data suggest that cell-based therapies have the potential to improve stroke outcomes.

Methods: Eighteen patients with stable, chronic stroke were enrolled in a 2-year, open-label, single-arm study to evaluate the safety and clinical outcomes of surgical transplantation of modified bone marrow-derived mesenchymal stem cells (SB623).

Results: All patients in the safety population (N=18) experienced at least 1 treatment-emergent adverse event. Six patients experienced 6 serious treatment-emergent adverse events; 2 were probably or definitely related to surgical procedure; none were related to cell treatment. All serious treatment-emergent adverse events resolved without sequelae. There were no dose-limiting toxicities or deaths. Sixteen patients completed 12 months of follow-up at the time of this analysis. Significant improvement from baseline (mean) was reported for: (1) European Stroke Scale: mean increase 6.88 (95% confidence interval, 3.5-10.3; P<0.001), (2) National Institutes of Health Stroke Scale: mean decrease 2.00 (95% confidence interval, -2.7 to -1.3; P<0.001), (3) Fugl-Meyer total score: mean increase 19.20 (95% confidence interval, 11.4-27.0; P<0.001), and (4) Fugl-Meyer motor function total score: mean increase 11.40 (95% confidence interval, 4.6-18.2; P<0.001). No changes were observed in modified Rankin Scale. The area of magnetic resonance T2 fluid-attenuated inversion recovery signal change in the ipsilateral cortex 1 week after implantation significantly correlated with clinical improvement at 12 months (P<0.001 for European Stroke Scale).

Conclusions: In this interim report, SB623 cells were safe and associated with improvement in clinical outcome end points at 12 months.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01287936.

Keywords: Notch 1; allogeneic transplantation; mesenchymal stromal cells; phase 1 clinical trial; stem cells; stereotactic techniques; stroke.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bone Marrow Transplantation / methods*
  • Female
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Middle Aged
  • Stroke / surgery*
  • Treatment Outcome

Associated data

  • ClinicalTrials.gov/NCT01287936