title: Therapeutic effect of human umbilical tissue-derived cell treatment in rats with experimental intracerebral hemorrhage.
abstract: OBJECTIVE
  The present study examines whether human umbilical tissue-derived cells (hUTC) have a neuro-restorative effect and improve functional recovery after intracerebral hemorrhage (ICH) in rats.
  
  
  METHODS
  Primary ICH was induced in male Wistar rats by stereotactic injection of 100μL of autologous blood into the striatal region adjacent to the subventricular zone. Briefly, the rats were randomly divided into six groups, each group was intravenously injected either with 2mL phosphate-buffered saline (PBS) or 3million hUTC in PBS at 1, 3 or 7days after ICH (n=8/group). To evaluate neurological functional outcome, each animal was subjected to the modified neurological severity score (mNSS) and corner turn tests at different time points after ICH. At four weeks post treatment, each group was anesthetized intraperitoneally, sacrificed, and brain tissues were processed histologically. Immunohistochemistry was employed to measure vascularity (vWF), neurogenesis (BrdU TUJ1, DCX and NeuN), synaptogenesis (synaptophysin) and apoptosis (TUNEL).
  
  
  RESULTS
  The hUTC-treated animals showed significantly improved neurological functional outcomes as assessed by mNSS and corner turn tests at 14, 21 and 28days post-injection in each treatment group (P<0.05) as compared to the PBS controls. Animals treated with hUTC were seen to have significantly increased cell proliferation, vascularity and synaptogenesis, as well as reduced apoptosis in the hematoma rim compared to the corresponding control group (P<0.05).
  
  
  CONCLUSIONS
  Intravenously infused hUTC have a beneficial effect after experimental ICH by functional and histochemical measurements of neural cell proliferation and synaptogenesis in the ICH border zone. This brain region also shows correlative evidence of neuronal recovery with increased vascularity.
authors.affiliation: Department of Neurosurgery, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI 48202, USA.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Yang
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Han
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Seyda
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.forename: Donald M
authors.initials: DM
authors.lastname: Seyfried
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001973:Bromodeoxyuridine / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002543:Cerebral Hemorrhage / Q000601:surgery*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology*; D012720:Severity of Illness Index; D013234:Stem Cells / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology*; D014841:von Willebrand Factor
chemical_list: C000714328:DCX protein, human; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D016708:Synaptophysin; C498585:TUBB3 protein, human; D014404:Tubulin; D014841:von Willebrand Factor; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine