Autologous neural progenitor cell transplantation into newborn mice modeling for E200K genetic prion disease delays disease progression

Kati Frid, Orli Binyamin, Nina Fainstein, Guy Keller, Tamir Ben-Hur, Ruth Gabizon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

TgMHu2ME199K mice, a transgenic line mimicking genetic prion disease, are born healthy and gradually deteriorate to a terminal neurological condition concomitant with the accumulation of disease-related PrP. To investigate whether transplantation of neural progenitor cells (NPCs) to these mice can delay disease aggravation, we first tested the properties of mutant PrP in homogenates and enriched NPCs from TgMHu2ME199K embryos, as compared to PrP in sick TgMHu2ME199K brains. Next, we tested the clinical effect of NPCs transplantation into newborn TgMHu2ME199K mice. We show that mutant PrP does not convert into a disease-related isoform while in progenitor cells. Most important, transplantation of both wild type and transgenic NPCs significantly delayed the progression of spontaneous prion disease in TgMHu2ME199K mice. While the strong clinical effect was not accompanied by a reduced accumulation of disease-related PrP, treated mouse brains presented a significant reduction in amyloid glycosaminoglycans and preservation of neurogenesis levels, indicating a strong neuroprotective effect. These results may encourage the investigation of new pathways for treatment in these terrible diseases.

Original languageAmerican English
Pages (from-to)192-200
Number of pages9
JournalNeurobiology of Aging
Volume65
DOIs
StatePublished - May 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

  • Brain
  • Genetic diseases
  • Neuroprotection
  • Prion
  • Stem cells

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