title: Reparative therapy for acute ischemic stroke with allogeneic mesenchymal stem cells from adipose tissue: a safety assessment: a phase II randomized, double-blind, placebo-controlled, single-center, pilot clinical trial.
abstract: BACKGROUND
  Few studies have evaluated the possible beneficial effect of the administration of stem cells in the early stages of stroke. Intravenous administration of allogeneic mesenchymal stem cells (MSCs) from adipose tissue in patients with acute stroke could be a safe therapy for promoting neurovascular unit repair, consequently supporting better functional recovery. We aim to assess the safety and efficacy of MSC administration and evaluate its potential as a treatment for cerebral protection and repair.
  
  
  METHODS
  A Phase IIa, prospective, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Twenty patients presenting acute ischemic stroke will be randomized in a 1:1 proportion to treatment with allogeneic MSCs from adipose tissue or to placebo (or vehicle) administered as a single intravenous dose within the first 2 weeks after the onset of stroke symptoms. The patients will be followed up for 2 years. Primary outcomes for safety analysis: adverse events (AEs) and serious AEs; neurologic and systemic complications, and tumor development. Secondary outcomes for efficacy analysis: modified Rankin Scale; NIHSS; infarct size; and biochemical markers of brain repair (vascular endothelial growth factor, brain-derived neurotrophic factor, and matrix metalloproteinases 9).
  
  
  CONCLUSIONS
  To our knowledge, this is the first, phase II, pilot clinical trial to investigate the safety and efficacy of intravenous administration of allogeneic MSCs from adipose tissue within the first 2 weeks of stroke. In addition, its results will help us define the best criteria for a future phase III study.
authors.affiliation: Stroke Center, Department of Neurology, La Paz University Hospital, IdiPAZ Health Research Institute, Universidad Autónoma de Madrid, Madrid, Spain. Electronic address: exuperio.diez@salud.madrid.org.
authors.forename: Exuperio
authors.initials: E
authors.lastname: Díez-Tejedor
authors.affiliation: Stroke Center, Department of Neurology, La Paz University Hospital, IdiPAZ Health Research Institute, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Gutiérrez-Fernández
authors.affiliation: Stroke Center, Department of Neurology, La Paz University Hospital, IdiPAZ Health Research Institute, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Martínez-Sánchez
authors.affiliation: Stroke Center, Department of Neurology, La Paz University Hospital, IdiPAZ Health Research Institute, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Rodríguez-Frutos
authors.affiliation: Stroke Center, Department of Neurology, La Paz University Hospital, IdiPAZ Health Research Institute, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Ruiz-Ares
authors.affiliation: Stroke Center, Department of Neurology, La Paz University Hospital, IdiPAZ Health Research Institute, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Manuel Lara
authors.initials: ML
authors.lastname: Lara
authors.affiliation: Stroke Center, Department of Neurology, La Paz University Hospital, IdiPAZ Health Research Institute, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Blanca Fuentes
authors.initials: BF
authors.lastname: Gimeno
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000473:pathology / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007238:Infarction / Q000473:pathology; D007262:Infusions, Intravenous; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D020521:Stroke / Q000097:blood / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D042461:Vascular Endothelial Growth Factor A; C019277:brain-derived growth factor; D020780:Matrix Metalloproteinase 9
keywords: Acute ischemic stroke; clinical trial; reparative therapy; safety; stem cells