title: Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke.
abstract: OBJECTIVE
  To evaluate the quality of preclinical evidence for mesenchymal stromal cell (MSC) treatment of ischemic stroke, determine effect size of MSC therapy, and identify clinical measures that correlate with differences in MSC effects.
  
  
  METHODS
  A literature search identified studies of MSCs in animal models of cerebral ischemia. For each, a Quality Score was derived, and effect size of MSCs was determined for the most common behavioral and histologic endpoints.
  
  
  RESULTS
  Of 46 studies, 44 reported that MSCs significantly improved outcome. The median Quality Score was 5.5 (of 10). The median effect size was 1.78 for modified Neurological Severity Score, 1.73 for the adhesive removal test, 1.02 for the rotarod test, and 0.93 for infarct volume reduction. Quality Score correlated significantly and positively with effect size for the modified Neurological Severity Score. Effect sizes varied significantly with clinical measures such as administration route (intracerebral > intra-arterial > IV, although effect size for IV was nonetheless very large at 1.55) and species receiving MSCs (primate > rat > mouse). Because many MSC mechanisms are restorative, analyses were repeated examining only the 36 preclinical studies administering MSCs ≥ 24 hours poststroke; results were overall very similar.
  
  
  CONCLUSIONS
  In preclinical studies, MSCs have consistently improved multiple outcome measures, with very large effect sizes. Results were robust across species studied, administration route, species of MSC origin, timing, degree of immunogenicity, and dose, and in the presence of comorbidities. In contrast to meta-analyses of preclinical data for other stroke therapies, higher-quality MSC preclinical studies were associated with larger behavioral gains. These findings support the utility of further studies to translate MSCs in the treatment of ischemic stroke in humans.
authors.affiliation: From the Departments of Neurology and Anatomy & Neurobiology (Q.V., K.X., S.C.C.), Pharmaceutical Sciences, Biomedical Engineering, and Chao Family Comprehensive Cancer Center (M.E., W.Z.), and Sue and Bill Gross Stem Cell Research Center (Q.V., K.X., M.E., W.Z., S.C.C.), University of California, Irvine.
authors.forename: Quynh
authors.initials: Q
authors.lastname: Vu
authors.forename: Kate
authors.initials: K
authors.lastname: Xie
authors.forename: Mark
authors.initials: M
authors.lastname: Eckert
authors.forename: Weian
authors.initials: W
authors.lastname: Zhao
authors.forename: Steven C
authors.initials: SC
authors.lastname: Cramer
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000628:therapy*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D004195:Disease Models, Animal; D006801:Humans; D059630:Mesenchymal Stem Cells; D051379:Mice; D017063:Outcome Assessment, Health Care; D051381:Rats; D020127:Recovery of Function / Q000502:physiology; D020521:Stroke / Q000473:pathology / Q000628:therapy*