Differential fate and functional outcome of lithium chloride primed adult neural progenitor cell transplants in a rat model of Huntington diseaseReport as inadecuate




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Stem Cell Research and Therapy

, 1:41

First Online: 22 December 2010Received: 03 August 2010Accepted: 22 December 2010

Abstract

IntroductionThe ability to predetermine the fate of transplanted neural progenitor cells NPCs and specifically to direct their maturation has the potential to enhance the efficiency of cell-transplantation therapy for neurodegenerative disease. We previously demonstrated that transient exposure of subventricular zone SVZ-derived adult NPCs to lithium chloride during in vitro proliferation alters differential fate in vitro and increases the proportion of cells expressing neuronal markers while reducing glial progeny. To extend these findings, we examined whether in vitro priming of adult SVZ-derived NPCs with lithium chloride before transplantation into the quinolinic acid QA lesion rat model of Huntington disease altered in vivo neuronal differentiation and sensorimotor function compared with nonprimed NPC transplants.

MethodsNPCs were isolated from the SVZ of the adult rat brain and cultured for 2 weeks. Four days before transplantation into the QA-lesioned rat striatum, the cells were labeled with BrdU and primed with lithium chloride. The rats underwent regular evaluation of forelimb use and sensorimotor neglect to establish functional effects of NPC transplantation. Twelve weeks after transplantation, the brains were analyzed with immunohistochemistry to compare the differential fate of primed and nonprimed NPCs.

ResultsWe observed that in vitro priming of adult NPCs with lithium chloride reduced gliogenesis and enhanced the occurrence of DARPP-32-positive neurons when compared with nonprimed cells 12 weeks after transplantation into the QA-lesioned striatum. Lithium chloride priming also augmented the formation of efferent projections from newly formed neurons in the damaged host striatum to the globus pallidus. This was associated with acceleration of sensorimotor function recovery in rats receiving transplants of lithium chloride-primed adult NPCs compared with nonprimed transplants.

ConclusionsThese initial findings indicate that in vitro priming of adult NPCs with lithium chloride may augment transplant efficiency and accelerate sensorimotor function outcome in vivo.

AbbreviationsBDNFbrain-derived neurotrophic factor

HDHuntington disease

NPCneural progenitor cell

QAquinolinic acid

SVZsubventricular zone.

Electronic supplementary materialThe online version of this article doi:10.1186-scrt41 contains supplementary material, which is available to authorized users.

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Author: Elena M Vazey - Bronwen Connor

Source: https://link.springer.com/







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