title: Human induced pluripotent stem cells improve recovery in stroke-injured aged rats.
abstract: OBJECTIVE
  Induced pluripotent stem cells (iPSCs) improve behavior and form neurons after implantation into the stroke-injured adult rodent brain. How the aged brain responds to grafted iPSCs is unknown. We determined survival and differentiation of grafted human fibroblast-derived iPSCs and their ability to improve recovery in aged rats after stroke.
  
  
  METHODS
  Twenty-four months old rats were subjected to 30 min distal middle cerebral artery occlusion causing neocortical damage. After 48 h, animals were transplanted intracortically with human iPSC-derived long-term neuroepithelial-like stem (hiPSC-lt-NES) cells. Controls were subjected to stroke and were vehicle-injected.
  
  
  RESULTS
  Cell-grafted animals performed better than vehicle-injected recipients in cylinder test at 4 and 7 weeks. At 8 weeks, cell proliferation was low (0.7 %) and number of hiPSC-lt-NES cells corresponded to 49.2% of that of implanted cells. Transplanted cells expressed markers of neuroblasts and mature and GABAergic neurons. Cell-grafted rats exhibited less activated microglia/macrophages in injured cortex and neuronal loss was mitigated.
  
  
  CONCLUSIONS
  Our study provides the first evidence that grafted human iPSCs survive, differentiate to neurons and ameliorate functional deficits in stroke-injured aged brain.
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, Lund, Sweden.
authors.forename: Jemal
authors.initials: J
authors.lastname: Tatarishvili
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, Lund, Sweden.
authors.forename: Koichi
authors.initials: K
authors.lastname: Oki
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, Lund, Sweden.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Monni
authors.affiliation: Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn and Hertie Fundation, Bonn, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Koch
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, Lund, Sweden I. Javakhishvili Tbilisi State University, Tbilisi, Georgia.
authors.forename: Tamar
authors.initials: T
authors.lastname: Memanishvili
authors.affiliation: Department of Psychiatry and Molecular Psychiatry, Rostock University Medical School, Rostock, Germany.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Buga
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, Lund, Sweden.
authors.forename: Vivek
authors.initials: V
authors.lastname: Verma
authors.affiliation: Department of Psychiatry and Molecular Psychiatry, Rostock University Medical School, Rostock, Germany.
authors.forename: Aurel
authors.initials: A
authors.lastname: Popa-Wagner
authors.affiliation: Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn and Hertie Fundation, Bonn, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, Lund, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Lindvall
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, Lund, Sweden.
authors.forename: Zaal
authors.initials: Z
authors.lastname: Kokaia
mesh_terms: D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000601:surgery*; D002454:Cell Differentiation; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D051959:ELAV Proteins / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology* / Q000637:transplantation*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000089622:Doublecortin Domain Proteins; D051959:ELAV Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D042461:Vascular Endothelial Growth Factor A; D005680:gamma-Aminobutyric Acid; D010751:Phosphopyruvate Hydratase
keywords: Stroke; aging; inflammation; neural stem cell; neuroregeneration; recovery; reprogramming; transplantation