title: Late transplantation of allogeneic bone marrow stromal cells improves neurologic deficits subsequent to intracerebral hemorrhage.
abstract: OBJECTIVE
  Stem cell therapy seems to be a promising therapeutic tool for treating central nervous system (CNS) injuries. Bone marrow stromal cell (BMSC) transplantation influences functional outcome subsequent to intracerebral hemorrhage (ICH), and enhances endogenous neurogenesis in acute condition studies. We investigated whether late administration of BMSC improves functional deficits subsequent to ICH.
  
  
  METHODS
  Experimental ICH was induced by stereotactic injection of 0.5 IU collagenase type IV in the striatum of adult female Wistar rats, and 2 months later intralesional administration of 5 × 10(6) allogeneic BMSC from male donors rats in saline (n = 10), or saline only (n = 10), was performed. In the following 6 months, functional outcome was evaluated in each animal by rotarod, modified neurologic severity score (mNSS) and video-tracking box (VTB) tests. To study the behavior of BMSC after transplantation, in situ hybridization studies were performed, with double labeling of the chromosome Y-linked SrY-gene, and neuronal nuclei (NeuN) protein or gliofibrillary acidic protein (GFAP).
  
  
  RESULTS
  The assessment test revealed significant improvements in functional outcome for the BMSC-treated animals after 2 months of follow-up. Histologic results showed that functional outcome was associated with strong reactivation of endogenous neurogenesis. Furthermore, intralesional BMSC not only integrated in the injured tissue but also showed phenotypic expression of GFAP and NeuN.
  
  
  CONCLUSIONS
  Late intracerebral transplantation of allogeneic BMSC induces functional recovery after ICH. The possibility of using this type of cell therapy to reverse the consequences of hemorrhagic stroke in humans should be considered.
authors.affiliation: Neuroscience Research Unit, Service of Surgical Research, Hospital Puerta de Hierro-Majadahonda, Autonomous University, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Otero
authors.forename: Mercedes
authors.initials: M
authors.lastname: Zurita
authors.forename: Celia
authors.initials: C
authors.lastname: Bonilla
authors.forename: Concepcion
authors.initials: C
authors.lastname: Aguayo
authors.forename: Angela
authors.initials: A
authors.lastname: Vela
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Rico
authors.forename: Jesus
authors.initials: J
authors.lastname: Vaquero
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000032:analysis; D016026:Bone Marrow Transplantation; D002543:Cerebral Hemorrhage / Q000150:complications*; D005260:Female; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D009422:Nervous System Diseases / Q000209:etiology* / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar; D051876:Sex-Determining Region Y Protein / Q000032:analysis; D017154:Stromal Cells / Q000637:transplantation
chemical_list: D034961:Antigens, Nuclear; D009419:Nerve Tissue Proteins; C546339:Rbfox3 protein, rat; D051876:Sex-Determining Region Y Protein; C497747:Sry protein, rat