Cargando…

Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus

As clinical application of neural stem cell (NSC) grafting into the brain would also encompass aged people, critical evaluation of engraftment of NSC graft-derived cells in the aged hippocampus has significance. We examined the engraftment and differentiation of alkaline phosphatase-positive NSCs ex...

Descripción completa

Detalles Bibliográficos
Autores principales: Shetty, Ashok K., Hattiangady, Bharathi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AlphaMed Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996439/
https://www.ncbi.nlm.nih.gov/pubmed/27194744
http://dx.doi.org/10.5966/sctm.2015-0270
_version_ 1782449603389423616
author Shetty, Ashok K.
Hattiangady, Bharathi
author_facet Shetty, Ashok K.
Hattiangady, Bharathi
author_sort Shetty, Ashok K.
collection PubMed
description As clinical application of neural stem cell (NSC) grafting into the brain would also encompass aged people, critical evaluation of engraftment of NSC graft-derived cells in the aged hippocampus has significance. We examined the engraftment and differentiation of alkaline phosphatase-positive NSCs expanded from the postnatal subventricular zone (SVZ), 3 months after grafting into the intact young or aged rat hippocampus. Graft-derived cells engrafted robustly into both young and aged hippocampi. Although most graft-derived cells pervasively migrated into different hippocampal layers, the graft cores endured and contained graft-derived neurons expressing neuron-specific nuclear antigen (NeuN) and γ-amino butyric acid in both groups. A fraction of migrated graft-derived cells in the neurogenic subgranular zone-granule cell layer also expressed NeuN. Neuronal differentiation was, however, occasionally seen amid graft-derived cells that had migrated into non-neurogenic regions, where substantial fractions differentiated into S-100β+ astrocytes, NG2+ oligodendrocyte progenitors, or Olig2+ putative oligodendrocytes. In both age groups, graft cores located in non-neurogenic regions displayed many doublecortin-positive (DCX+) immature neurons at 3 months after grafting. Analyses of cells within graft cores using birth dating and putative NSC markers revealed that DCX+ neurons were newly born neurons derived from engrafted cells and that putative NSCs persisted within the graft cores. Thus, both young and aged hippocampi support robust engraftment and similar differentiation of SVZ-NSC graft-derived cells. Furthermore, some grafted NSCs retain the “stemness” feature and produce new neurons even at 3 months after grafting, implying that grafting of SVZ-NSCs into the young or aged hippocampus leads to establishment of new neurogenic niches in non-neurogenic regions. SIGNIFICANCE: The results demonstrate that advanced age of the host at the time of grafting has no major adverse effects on engraftment, migration, and differentiation of grafted subventricular zone-neural stem cells (SVZ-NSCs) in the intact hippocampus, as both young and aged hippocampi promoted excellent engraftment, migration, and differentiation of SVZ-NSC graft-derived cells in the present study. Furthermore, SVZ-NSC grafts showed ability for establishing neurogenic niches in non-neurogenic regions, generating new neurons for extended periods after grafting. This phenomenon will be beneficial if these niches can continuously generate new neurons and glia in the grafted hippocampus, as newly generated neurons and glia are expected to improve, not only the microenvironment, but also the plasticity and function of the aged hippocampus. Overall, these results have significance because the potential application of NSC grafting for treatment of neurodegenerative disorders at early stages of disease progression and age-related impairments would mostly involve aged persons as recipients.
format Online
Article
Text
id pubmed-4996439
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher AlphaMed Press
record_format MEDLINE/PubMed
spelling pubmed-49964392017-03-01 Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus Shetty, Ashok K. Hattiangady, Bharathi Stem Cells Transl Med Tissue-Specific Progenitor and Stem Cells As clinical application of neural stem cell (NSC) grafting into the brain would also encompass aged people, critical evaluation of engraftment of NSC graft-derived cells in the aged hippocampus has significance. We examined the engraftment and differentiation of alkaline phosphatase-positive NSCs expanded from the postnatal subventricular zone (SVZ), 3 months after grafting into the intact young or aged rat hippocampus. Graft-derived cells engrafted robustly into both young and aged hippocampi. Although most graft-derived cells pervasively migrated into different hippocampal layers, the graft cores endured and contained graft-derived neurons expressing neuron-specific nuclear antigen (NeuN) and γ-amino butyric acid in both groups. A fraction of migrated graft-derived cells in the neurogenic subgranular zone-granule cell layer also expressed NeuN. Neuronal differentiation was, however, occasionally seen amid graft-derived cells that had migrated into non-neurogenic regions, where substantial fractions differentiated into S-100β+ astrocytes, NG2+ oligodendrocyte progenitors, or Olig2+ putative oligodendrocytes. In both age groups, graft cores located in non-neurogenic regions displayed many doublecortin-positive (DCX+) immature neurons at 3 months after grafting. Analyses of cells within graft cores using birth dating and putative NSC markers revealed that DCX+ neurons were newly born neurons derived from engrafted cells and that putative NSCs persisted within the graft cores. Thus, both young and aged hippocampi support robust engraftment and similar differentiation of SVZ-NSC graft-derived cells. Furthermore, some grafted NSCs retain the “stemness” feature and produce new neurons even at 3 months after grafting, implying that grafting of SVZ-NSCs into the young or aged hippocampus leads to establishment of new neurogenic niches in non-neurogenic regions. SIGNIFICANCE: The results demonstrate that advanced age of the host at the time of grafting has no major adverse effects on engraftment, migration, and differentiation of grafted subventricular zone-neural stem cells (SVZ-NSCs) in the intact hippocampus, as both young and aged hippocampi promoted excellent engraftment, migration, and differentiation of SVZ-NSC graft-derived cells in the present study. Furthermore, SVZ-NSC grafts showed ability for establishing neurogenic niches in non-neurogenic regions, generating new neurons for extended periods after grafting. This phenomenon will be beneficial if these niches can continuously generate new neurons and glia in the grafted hippocampus, as newly generated neurons and glia are expected to improve, not only the microenvironment, but also the plasticity and function of the aged hippocampus. Overall, these results have significance because the potential application of NSC grafting for treatment of neurodegenerative disorders at early stages of disease progression and age-related impairments would mostly involve aged persons as recipients. AlphaMed Press 2016-09 2016-05-18 /pmc/articles/PMC4996439/ /pubmed/27194744 http://dx.doi.org/10.5966/sctm.2015-0270 Text en ©AlphaMed Press
spellingShingle Tissue-Specific Progenitor and Stem Cells
Shetty, Ashok K.
Hattiangady, Bharathi
Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus
title Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus
title_full Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus
title_fullStr Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus
title_full_unstemmed Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus
title_short Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus
title_sort grafted subventricular zone neural stem cells display robust engraftment and similar differentiation properties and form new neurogenic niches in the young and aged hippocampus
topic Tissue-Specific Progenitor and Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996439/
https://www.ncbi.nlm.nih.gov/pubmed/27194744
http://dx.doi.org/10.5966/sctm.2015-0270
work_keys_str_mv AT shettyashokk graftedsubventricularzoneneuralstemcellsdisplayrobustengraftmentandsimilardifferentiationpropertiesandformnewneurogenicnichesintheyoungandagedhippocampus
AT hattiangadybharathi graftedsubventricularzoneneuralstemcellsdisplayrobustengraftmentandsimilardifferentiationpropertiesandformnewneurogenicnichesintheyoungandagedhippocampus