title: Stroke alters behavior of human skin-derived neural progenitors after transplantation adjacent to neurogenic area in rat brain.
abstract: Intracerebral transplantation of human induced pluripotent stem cells (iPSCs) can ameliorate behavioral deficits in animal models of stroke. How the ischemic lesion affects the survival of the transplanted cells, their proliferation, migration, differentiation, and function is only partly understood.
  
  
  
  Here we have assessed the influence of the stroke-induced injury on grafts of human skin iPSCs-derived long-term neuroepithelial-like stem cells using transplantation into the rostral migratory stream (RMS), adjacent to the neurogenic subventricular zone, in adult rats as a model system.
  
  
  
  We show that the occurrence of an ischemic lesion, induced by middle cerebral artery occlusion, in the striatum close to the transplant does not alter the survival, proliferation, or generation of neuroblasts or mature neurons or astrocytes from the grafted progenitors. In contrast, the migration and axonal projection patterns of the transplanted cells are markedly influenced. In the intact brain, the grafted cells send many fibers to the main olfactory bulb through the RMS and a few of them migrate in the same direction, reaching the first one third of this pathway. In the stroke-injured brain, on the other hand, the grafted cells only migrate toward the ischemic lesion and virtually no axonal outgrowth is observed in the RMS.
  
  
  
  Our findings indicate that signals released from the stroke-injured area regulate the migration of and fiber outgrowth from grafted human skin-derived neural progenitors and overcome the influence on these cellular properties exerted by the neurogenic area/RMS in the intact brain.
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, 221 84, Lund, Sweden.|Present address: Laboratory of Human Neuroanatomy, Department of Health Sciences, Faculty of Medicine, CRIB, University of Castilla-La Mancha, 02008, Albacete, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: de la Rosa-Prieto
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, 221 84, Lund, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Laterza
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, 221 84, Lund, Sweden.
authors.forename: Ana
authors.initials: A
authors.lastname: Gonzalez-Ramos
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, 221 84, Lund, Sweden.
authors.forename: Somsak
authors.initials: S
authors.lastname: Wattananit
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, 221 84, Lund, Sweden.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Ge
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, 221 84, 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, 221 84, Lund, Sweden. daniel.tornero@med.lu.se.
authors.forename: Daniel
authors.identifier: 0000-0002-4812-4091
authors.initials: D
authors.lastname: Tornero
authors.affiliation: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, 221 84, Lund, Sweden.
authors.forename: Zaal
authors.initials: Z
authors.lastname: Kokaia
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D020244:Infarction, Middle Cerebral Artery; D058953:Neural Stem Cells / Q000276:immunology / Q000637:transplantation*; D055495:Neurogenesis; D009474:Neurons / Q000276:immunology / Q000473:pathology; D051381:Rats; D020521:Stroke / Q000276:immunology / Q000473:pathology / Q000628:therapy*
keywords: Adult neurogenesis; Human skin-derived cells; Pluripotent; Rostral migratory stream; Stroke; Subventricular zone; Transplantation