title: Delayed administration of human umbilical tissue-derived cells improved neurological functional recovery in a rodent model of focal ischemia.
abstract: OBJECTIVE
  The short time window required by neuroprotective strategies for successful treatment of patients with ischemic stroke precludes treatment for most. However, clinical therapies based on neuroregeneration might extend this therapeutic time window and thus address a significant unmet need. Human umbilical tissue-derived cells have shown great potential as neuroregenerative candidates for stroke treatment.
  
  
  METHODS
  The effectiveness of intravenous administration of human umbilical tissue-derived cells was tested in a rodent middle cerebral artery stroke model in a dose escalation study (doses tested: 3×10(5), 1×10(6), 3×x10(6), or 1×10(7) cells/injection) followed by a time-of-administration study (time after stroke: Day 1, Day 7, Day 30, and Day 90 at a dose of 5×10(6) cells/injection). Controls were phosphate-buffered saline injections and human bone marrow-derived mesenchymal stromal cell injections. Post-treatment outcome tools included the modified neurological severity score and the adhesive removal tests. Histology was performed on all cases to evaluate synaptogenesis, neurogenesis, angiogenesis, and cell apoptosis.
  
  
  RESULTS
  Statistically significant improvements of human umbilical tissue-derived cell treatment versus phosphate-buffered saline in modified neurological severity scores and adhesive test results were observed for doses≥3×10(6) cells up to 30 days poststroke. At doses≥3×10(6), histological evaluations confirmed enhanced synaptogenesis, vessel density, and reduced apoptosis in the ischemic boundary zone and increased proliferation of progenitor cells in the subventricular zone of human umbilical tissue-derived cell-treated animals versus phosphate-buffered saline controls.
  
  
  CONCLUSIONS
  These results indicate effectiveness of intravenous administration of human umbilical tissue-derived cells in a rodent stroke model compared with phosphate-buffered saline control and warrant further investigation for possible use in humans.
authors.affiliation: Department of Neurology, Henry Ford Hospital, 2799 W Grand Boulevard, Detroit, MI 48202, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.forename: Anna
authors.initials: A
authors.lastname: Gosiewska
authors.forename: Klaudyne
authors.initials: K
authors.lastname: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D007275:Injections, Intravenous; D008297:Male; D059630:Mesenchymal Stem Cells; D018919:Neovascularization, Physiologic / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology*; D013234:Stem Cells; D013997:Time Factors; D014470:Umbilical Cord / Q000166:cytology*