Stroke alters behavior of human skin-derived neural progenitors after transplantation adjacent to neurogenic area in rat brain

Carlos De La Rosa-Prieto, Cecilia Laterza, Ana Gonzalez-Ramos, Somsak Wattananit, Ruimin Ge, Olle Lindvall, Daniel Tornero, Zaal Kokaia

Research output: Contribution to journalArticlepeer-review

8 Citations (SciVal)

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Article number59
JournalStem Cell Research and Therapy
Volume8
Issue number1
DOIs
Publication statusPublished - 2017 Mar 9

Subject classification (UKÄ)

  • Neurology

Keywords

  • Adult neurogenesis
  • Human skin-derived cells
  • Pluripotent
  • Rostral migratory stream
  • Stroke
  • Subventricular zone
  • Transplantation

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