title: Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke.
abstract: Treatment with CD34+ hematopoietic stem/progenitor cells has been shown to improve functional recovery in nonhuman models of ischemic stroke via promotion of angiogenesis and neurogenesis. We aimed to determine the safety and feasibility of treatment with CD34+ cells delivered intra-arterially in patients with acute ischemic stroke. This was the first study in human subjects. We performed a prospective, nonrandomized, open-label, phase I study of autologous, immunoselected CD34+ stem/progenitor cell therapy in patients presenting within 7 days of onset with severe anterior circulation ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score≥8). CD34+ cells were collected from the bone marrow of the subjects before being delivered by catheter angiography into the ipsilesional middle cerebral artery. Eighty-two patients with severe anterior circulation ischemic stroke were screened, of whom five proceeded to treatment. The common reasons for exclusion were age>80 years (n=19); medical instability (n=17), and significant carotid stenosis (n=13). The procedure was well tolerated in all patients, and no significant treatment-related adverse effects occurred. All patients showed improvements in clinical functional scores (Modified Rankin Score and NIHSS score) and reductions in lesion volume during a 6-month follow-up period. Autologous CD34+ selected stem/progenitor cell therapy delivered intra-arterially into the infarct territory can be achieved safely in patients with acute ischemic stroke. Future studies that address eligibility criteria, dosage, delivery site, and timing and that use surrogate imaging markers of outcome are desirable before larger scale clinical trials.
authors.affiliation: Department of Stroke Medicine, Clinical Neurosciences, Department of Interventional Radiology, Stem Cell Transplant Unit, and Department of Haematology, Imperial College Healthcare National Health Services Trust, London, United Kingdom; Departments of Surgery and Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Services Foundation Trust, London, United Kingdom; Institute of Neurology, University College London, London, United Kingdom sbanerjee73@hotmail.com.
authors.forename: Soma
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Stroke Medicine, Clinical Neurosciences, Department of Interventional Radiology, Stem Cell Transplant Unit, and Department of Haematology, Imperial College Healthcare National Health Services Trust, London, United Kingdom; Departments of Surgery and Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Services Foundation Trust, London, United Kingdom; Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Bentley
authors.affiliation: Department of Stroke Medicine, Clinical Neurosciences, Department of Interventional Radiology, Stem Cell Transplant Unit, and Department of Haematology, Imperial College Healthcare National Health Services Trust, London, United Kingdom; Departments of Surgery and Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Services Foundation Trust, London, United Kingdom; Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hamady
authors.affiliation: Department of Stroke Medicine, Clinical Neurosciences, Department of Interventional Radiology, Stem Cell Transplant Unit, and Department of Haematology, Imperial College Healthcare National Health Services Trust, London, United Kingdom; Departments of Surgery and Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Services Foundation Trust, London, United Kingdom; Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Marley
authors.affiliation: Department of Stroke Medicine, Clinical Neurosciences, Department of Interventional Radiology, Stem Cell Transplant Unit, and Department of Haematology, Imperial College Healthcare National Health Services Trust, London, United Kingdom; Departments of Surgery and Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Services Foundation Trust, London, United Kingdom; Institute of Neurology, University College London, London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Davis
authors.affiliation: Department of Stroke Medicine, Clinical Neurosciences, Department of Interventional Radiology, Stem Cell Transplant Unit, and Department of Haematology, Imperial College Healthcare National Health Services Trust, London, United Kingdom; Departments of Surgery and Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Services Foundation Trust, London, United Kingdom; Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Abdul
authors.initials: A
authors.lastname: Shlebak
authors.affiliation: Department of Stroke Medicine, Clinical Neurosciences, Department of Interventional Radiology, Stem Cell Transplant Unit, and Department of Haematology, Imperial College Healthcare National Health Services Trust, London, United Kingdom; Departments of Surgery and Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Services Foundation Trust, London, United Kingdom; Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Nicholls
authors.affiliation: Department of Stroke Medicine, Clinical Neurosciences, Department of Interventional Radiology, Stem Cell Transplant Unit, and Department of Haematology, Imperial College Healthcare National Health Services Trust, London, United Kingdom; Departments of Surgery and Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Services Foundation Trust, London, United Kingdom; Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Williamson
authors.affiliation: Department of Stroke Medicine, Clinical Neurosciences, Department of Interventional Radiology, Stem Cell Transplant Unit, and Department of Haematology, Imperial College Healthcare National Health Services Trust, London, United Kingdom; Departments of Surgery and Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Services Foundation Trust, London, United Kingdom; Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Steen L
authors.initials: SL
authors.lastname: Jensen
authors.affiliation: Department of Stroke Medicine, Clinical Neurosciences, Department of Interventional Radiology, Stem Cell Transplant Unit, and Department of Haematology, Imperial College Healthcare National Health Services Trust, London, United Kingdom; Departments of Surgery and Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Services Foundation Trust, London, United Kingdom; Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Myrtle
authors.initials: M
authors.lastname: Gordon
authors.affiliation: Department of Stroke Medicine, Clinical Neurosciences, Department of Interventional Radiology, Stem Cell Transplant Unit, and Department of Haematology, Imperial College Healthcare National Health Services Trust, London, United Kingdom; Departments of Surgery and Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Services Foundation Trust, London, United Kingdom; Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Nagy
authors.initials: N
authors.lastname: Habib
authors.affiliation: Department of Stroke Medicine, Clinical Neurosciences, Department of Interventional Radiology, Stem Cell Transplant Unit, and Department of Haematology, Imperial College Healthcare National Health Services Trust, London, United Kingdom; Departments of Surgery and Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Services Foundation Trust, London, United Kingdom; Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Chataway
mesh_terms: D000208:Acute Disease; D000368:Aged; D018952:Antigens, CD34; D064592:Autografts; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000628:therapy*; D002533:Cerebral Angiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D033581:Stem Cell Transplantation; D020521:Stroke / Q000000981:diagnostic imaging / Q000628:therapy*
chemical_list: D018952:Antigens, CD34
keywords: CD34+; Intra-arterial; Ischemic stroke; Stem cells
references.citation: J Cereb Blood Flow Metab. 2007 Jan;27(1):6-13
references.pmid: 16596121
references.citation: Neurosci Lett. 2003 Jun 5;343(2):129-33
references.pmid: 12759181
references.citation: Cell Transplant. 2012;21 Suppl 1:S13-21
references.pmid: 22507676
references.citation: J Clin Invest. 2004 Aug;114(3):330-8
references.pmid: 15286799
references.citation: Stroke. 2012 Feb;43(2):405-11
references.pmid: 22198983
references.citation: Regen Med. 2011 Jan;6(1):45-52
references.pmid: 21175286
references.citation: Lancet. 2012 Jun 23;379(9834):2352-63
references.pmid: 22632908
references.citation: Brain. 2011 Jun;134(Pt 6):1790-807
references.pmid: 21493695
references.citation: Stem Cell Rev Rep. 2011 Nov;7(4):1031-40
references.pmid: 21475954
references.citation: Neurology. 2001 Jun 26;56(12):1666-72
references.pmid: 11425931
references.citation: Stem Cells Dev. 2009 Jun;18(5):683-92
references.pmid: 19099374
references.citation: Lancet. 1991 Jun 22;337(8756):1521-6
references.pmid: 1675378
references.citation: J Cereb Blood Flow Metab. 2000 Sep;20(9):1311-9
references.pmid: 10994853
references.citation: J Neurosci. 2006 Mar 29;26(13):3444-53
references.pmid: 16571751
references.citation: J Neurol. 2007 Mar;254(3):327-32
references.pmid: 17345048
references.citation: Ann Neurol. 2005 Jun;57(6):874-82
references.pmid: 15929052
references.citation: Stem Cells. 2012 Apr;30(4):785-96
references.pmid: 22213183
references.citation: Ann Neurol. 2011 Jul;70(1):59-69
references.pmid: 21786299
references.citation: Neurorehabil Neural Repair. 2009 Nov;23(9):895-909
references.pmid: 19633272
references.citation: Circulation. 2004 Sep 28;110(13):1847-54
references.pmid: 15381647
references.citation: Exp Neurol. 1998 Feb;149(2):310-21
references.pmid: 9500961
references.citation: Eur J Haematol. 2005 Dec;75(6):461-7
references.pmid: 16313257
references.citation: Stroke. 2001 Apr;32(4):1005-11
references.pmid: 11283404
references.citation: Brain Res. 2004 Aug 6;1016(2):145-53
references.pmid: 15246850
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11839-44
references.pmid: 15280535
references.citation: Restor Neurol Neurosci. 2009;27(3):151-61
references.pmid: 19531871
references.citation: Stroke. 2012 Aug;43(8):2242-4
references.pmid: 22764211
references.citation: Stroke. 2003 Mar;34(3):745-51
references.pmid: 12624302
references.citation: J Neurosurg. 2005 Jul;103(1):38-45
references.pmid: 16121971
references.citation: Neurology. 2002 Aug 27;59(4):514-23
references.pmid: 12196642
references.citation: Neurosci Lett. 2008 Aug 8;440(3):246-50
references.pmid: 18572314
references.citation: Neurology. 2000 Aug 22;55(4):565-9
references.pmid: 10953194