title: Intravenous Autologous Bone Marrow Mononuclear Cell Transplantation for Stroke: Phase1/2a Clinical Trial in a Homogeneous Group of Stroke Patients.
abstract: The goal of this clinical trial was to assess the feasibility and safety of transplanting autologous bone marrow mononuclear cells into patients suffering severe embolic stroke. Major inclusion criteria included patients with cerebral embolism, age 20-75 years, National Institute of Health Stroke Scale (NIHSS) score displaying improvement of ≤ 5 points during the first 7 days after stroke, and NIHSS score of ≥ 10 on day 7 after stroke. Bone marrow aspiration (25 or 50 mL; N = 6 patients in each case) was performed 7-10 days poststroke, and bone marrow mononuclear cells were administrated intravenously. Mean total transplanted cell numbers were 2.5 × 10(8) and 3.4 × 10(8) cells in the lower and higher dose groups, respectively. No apparent adverse effects of administering bone marrow cells were observed. Compared with the lower dose, patients receiving the higher dose of bone marrow cells displayed a trend toward improved neurologic outcomes. Compared with 1 month after treatment, patients receiving cell therapy displayed a trend toward improved cerebral blood flow and metabolic rate of oxygen consumption 6 months after treatment. In comparison with historical controls, patients receiving cell therapy had significantly better neurologic outcomes. Our results indicated that intravenous transplantation of autologous bone marrow mononuclear cells is safe and feasible. Positive results and trends favoring neurologic recovery and improvement in cerebral blood flow and metabolism by cell therapy underscore the relevance of larger scale randomized controlled trials using this approach.
authors.affiliation: 1 Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation , Kobe, Japan .|2 Department of Neurology, National Cerebral and Cardiovascular Center , Suita, Japan .
authors.forename: Akihiko
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: 3 Department of Endovascular Therapy, Institute of Biomedical Research and Innovation , Kobe, Japan .|4 Department of Neurosurgery, Kobe City Medical Center General Hospital , Kobe, Japan .
authors.forename: Chiaki
authors.initials: C
authors.lastname: Sakai
authors.affiliation: 5 Department of Hematology, Hyogo College of Medicine , Nishinomiya, Japan .
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Soma
authors.affiliation: 1 Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation , Kobe, Japan .
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kasahara
authors.affiliation: 6 Executive Dean's Office, University of Tennessee , Memphis, Tennessee.
authors.forename: David M
authors.initials: DM
authors.lastname: Stern
authors.affiliation: 2 Department of Neurology, National Cerebral and Cardiovascular Center , Suita, Japan .
authors.forename: Katsufumi
authors.initials: K
authors.lastname: Kajimoto
authors.affiliation: 1 Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation , Kobe, Japan .|2 Department of Neurology, National Cerebral and Cardiovascular Center , Suita, Japan .
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.affiliation: 7 Department of Biostatistics, Hyogo College of Medicine , Nishinomiya, Japan .
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.affiliation: 8 Department of Regenerative Medicine, National Cerebral and Cardiovascular Center , Suita, Japan .
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamahara
authors.affiliation: 9 Department of Nursing, National Cerebral and Cardiovascular Center , Suita, Japan .
authors.forename: Kaori
authors.initials: K
authors.lastname: Doi
authors.affiliation: 10 Department of Neurology, Kobe City Medical Center General Hospital , Kobe, Japan .
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kohara
authors.affiliation: 11 Department of Neurology, Nishinomiya Kyoritsu Neurosurgical Hospital , Nishinomiya, Japan .
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishimura
authors.affiliation: 12 Institute for Advanced Medical Sciences, Hyogo College of Medicine , Nishinomiya, Japan .
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuyama
authors.affiliation: 2 Department of Neurology, National Cerebral and Cardiovascular Center , Suita, Japan .
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Naritomi
authors.affiliation: 3 Department of Endovascular Therapy, Institute of Biomedical Research and Innovation , Kobe, Japan .|4 Department of Neurosurgery, Kobe City Medical Center General Hospital , Kobe, Japan .
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sakai
authors.affiliation: 2 Department of Neurology, National Cerebral and Cardiovascular Center , Suita, Japan .
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nagatsuka
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D018952:Antigens, CD34 / Q000097:blood; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D002560:Cerebrovascular Circulation; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood / Q000378:metabolism; D012008:Recurrence; D020521:Stroke / Q000628:therapy*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D010100:Oxygen