Cell origin and culture history determine successful integration of neural precursor transplants into the dentate gyrus of the adult rat.

The success of transplants of neural tissue into the adult dentate gyrus in generating mature neurons is highly variable. Here we address the roles of the origin of the tissue and its pre-implantation preparation, and show that both are critical. We transplanted neonatal cultured or primary rat cell...

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Main Authors: Xia Chen, Aviva M Tolkovsky, Joe Herbert
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-02-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3040198?pdf=render
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author Xia Chen
Aviva M Tolkovsky
Joe Herbert
author_facet Xia Chen
Aviva M Tolkovsky
Joe Herbert
author_sort Xia Chen
collection DOAJ
description The success of transplants of neural tissue into the adult dentate gyrus in generating mature neurons is highly variable. Here we address the roles of the origin of the tissue and its pre-implantation preparation, and show that both are critical. We transplanted neonatal cultured or primary rat cells from either the ventral subventricular zone (vSVZ) or the dentate gyrus (DG) into the adult rat DG. Only primary DG cells robustly generated DG neurons (80% NeuN and Prox1-positive cells at 6 weeks), substantially repaired the damaged DG, and formed glutamatergic projections to the target CA3 region. Cultured DG cells expanded for 7 days showed limited neuronal differentiation after transplantation (10% NeuN and Prox1-positive cells) whereas cultured or primary vSVZ cells failed to make any Prox1-positive DG granular neurons. We found that a specific population of postmitotic young neurons (triple doublecortin/NeuN/Prox1-positive) were particularly abundant in primary DG cells, but were markedly reduced in the cultured DG cells and were absent in the cultured and primary vSVZ cells. Labelling of primary DG cells with the mitotic marker BrdU suggested that postmitotic young neurons are the source of the transplanted mature neurons in-vivo. We conclude that both the origin and pre-transplantation history of donor cells are key factors that determine the outcome of transplantation. These findings may be of therapeutic interest for cell replacement therapy in treating the damaged hippocampus.
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spelling doaj.art-8bdb474edfdd447ab3bb75e7e990dd732022-12-22T03:11:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-02-0162e1707210.1371/journal.pone.0017072Cell origin and culture history determine successful integration of neural precursor transplants into the dentate gyrus of the adult rat.Xia ChenAviva M TolkovskyJoe HerbertThe success of transplants of neural tissue into the adult dentate gyrus in generating mature neurons is highly variable. Here we address the roles of the origin of the tissue and its pre-implantation preparation, and show that both are critical. We transplanted neonatal cultured or primary rat cells from either the ventral subventricular zone (vSVZ) or the dentate gyrus (DG) into the adult rat DG. Only primary DG cells robustly generated DG neurons (80% NeuN and Prox1-positive cells at 6 weeks), substantially repaired the damaged DG, and formed glutamatergic projections to the target CA3 region. Cultured DG cells expanded for 7 days showed limited neuronal differentiation after transplantation (10% NeuN and Prox1-positive cells) whereas cultured or primary vSVZ cells failed to make any Prox1-positive DG granular neurons. We found that a specific population of postmitotic young neurons (triple doublecortin/NeuN/Prox1-positive) were particularly abundant in primary DG cells, but were markedly reduced in the cultured DG cells and were absent in the cultured and primary vSVZ cells. Labelling of primary DG cells with the mitotic marker BrdU suggested that postmitotic young neurons are the source of the transplanted mature neurons in-vivo. We conclude that both the origin and pre-transplantation history of donor cells are key factors that determine the outcome of transplantation. These findings may be of therapeutic interest for cell replacement therapy in treating the damaged hippocampus.http://europepmc.org/articles/PMC3040198?pdf=render
spellingShingle Xia Chen
Aviva M Tolkovsky
Joe Herbert
Cell origin and culture history determine successful integration of neural precursor transplants into the dentate gyrus of the adult rat.
PLoS ONE
title Cell origin and culture history determine successful integration of neural precursor transplants into the dentate gyrus of the adult rat.
title_full Cell origin and culture history determine successful integration of neural precursor transplants into the dentate gyrus of the adult rat.
title_fullStr Cell origin and culture history determine successful integration of neural precursor transplants into the dentate gyrus of the adult rat.
title_full_unstemmed Cell origin and culture history determine successful integration of neural precursor transplants into the dentate gyrus of the adult rat.
title_short Cell origin and culture history determine successful integration of neural precursor transplants into the dentate gyrus of the adult rat.
title_sort cell origin and culture history determine successful integration of neural precursor transplants into the dentate gyrus of the adult rat
url http://europepmc.org/articles/PMC3040198?pdf=render
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