Delay of gCJD aggravation in sick TgMHu2ME199K mice by combining NPC transplantation and Nano-PSO administration

gCJD is a fatal late-onset neurodegenerative disease linked to mutations in the PRNP gene. We have previously shown that transplantation of neural precursor cells (NPCs), or administration of a nanoformulation of pomegranate seed oil (Nano-PSO, GranaGard), into newborn asymptomatic TgMHu2ME199K mice...

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Bibliographic Details
Published in:	Neurobiology of aging Vol. 95; pp. 231 - 239
Main Authors:	Frid, Kati, Binyamin, Orli, Usman, Areen, Gabizon, Ruth
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-11-2020
Subjects:	Creutzfeldt-Jakob disease (CJD) Nano-Pomegranate Seed Oil (Nano-PSO) Neural precursor cells (NPCs) Prion Stem cells Transplantation Creutzfeldt-Jakob disease (CJD) Prion Transplantation Nano-Pomegranate Seed Oil (Nano-PSO) Neural precursor cells (NPCs) Stem cells
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Summary:	gCJD is a fatal late-onset neurodegenerative disease linked to mutations in the PRNP gene. We have previously shown that transplantation of neural precursor cells (NPCs), or administration of a nanoformulation of pomegranate seed oil (Nano-PSO, GranaGard), into newborn asymptomatic TgMHu2ME199K mice modeling for E200K gCJD significantly delayed the advance of clinical disease. In the present study, we tested the individual and combined effects of both treatments in older and sick TgMHu2ME199K mice. We show that while transplantation of NPCs at both initial (140 days) and advance clinical states (230 days) arrested disease progression for about 30 days, after which scores rapidly climbed to those of untreated Tgs, administration of Nano-PSO to transplanted TgMHu2ME199K mice resulted in detention of disease advance for 60-80 days, followed by a slower disease progression thereafter. Pathological examinations demonstrated the combined treatment extended the survival of the transplanted NPCs, and also increased the generation of endogenous stem cells. Our results suggest that administration of Nano-PSO may increase the beneficial effects of NPCs transplantation. [Display omitted] •Transplanting NPCs into genetic CJD mice arrests disease progression for 30–40 days.•The combined NPCs/Nano-PSO treatment doubled the period of disease arrest.•Nano-PSO prolonged the survival of transplanted NPCs, in addition to its neuroprotective effect.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0197-4580 1558-1497
DOI:	10.1016/j.neurobiolaging.2020.07.030