title: Clinical Outcomes of Transplanted Modified Bone Marrow-Derived Mesenchymal Stem Cells in Stroke: A Phase 1/2a Study.
abstract: Preclinical data suggest that cell-based therapies have the potential to improve stroke outcomes.
  
  
  
  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).
  
  
  
  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).
  
  
  
  In this interim report, SB623 cells were safe and associated with improvement in clinical outcome end points at 12 months.
  
  
  
  URL: https://www.clinicaltrials.gov. Unique identifier: NCT01287936.
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.). cerebral@stanford.edu.
authors.forename: Gary K
authors.initials: GK
authors.lastname: Steinberg
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
authors.forename: Douglas
authors.initials: D
authors.lastname: Kondziolka
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Wechsler
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
authors.forename: L Dade
authors.initials: LD
authors.lastname: Lunsford
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
authors.forename: Maria L
authors.initials: ML
authors.lastname: Coburn
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
authors.forename: Julia B
authors.initials: JB
authors.lastname: Billigen
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Kim
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
authors.forename: Jeremiah N
authors.initials: JN
authors.lastname: Johnson
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
authors.forename: Damien
authors.initials: D
authors.lastname: Bates
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
authors.forename: Bill
authors.initials: B
authors.lastname: King
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
authors.forename: Casey
authors.initials: C
authors.lastname: Case
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
authors.forename: Michael
authors.initials: M
authors.lastname: McGrogan
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
authors.forename: Ernest W
authors.initials: EW
authors.lastname: Yankee
authors.affiliation: From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
authors.forename: Neil E
authors.initials: NE
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D020521:Stroke / Q000601:surgery*; D016896:Treatment Outcome
keywords: Notch 1; allogeneic transplantation; mesenchymal stromal cells; phase 1 clinical trial; stem cells; stereotactic techniques; stroke