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Age is not a factor for SVZ-NSCs in the Hippocampus!

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Review of “Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus” from Stem Cells Translational Medicine by Stuart P. Atkinson

Studies suggest that grafting neural stem cells (NSCs) into the brain may lead to increased neurogenesis and, therefore, may represent an interesting therapeutic strategy for many different diseases and disorders. However, while neurogenesis in the subventricular zone (SVZ) of the forebrain is known to aid recovery from stroke or traumatic brain injury, less is known about consequences in the dentate gyrus (DG) of the hippocampus, the other “hotbed” of adult neurogenesis.

To fill this knowledge gap, researchers from the laboratory of Ashok K. Shetty (Texas A&M Health Science Center, USA) set out to study the consequences of SVZ-NSC transplantation into the hippocampus of both young and old rats. This new study, published in Stem Cells Translational Medicine, now shows that NSCs display similar advantageous activities in the young and old hippocampus and so may be an exciting therapeutic option [1]. It seems that age is not a factor for SVZ-NSCs in the hippocampus!

Initial examinations of the DG three months after transplantation found that both young and old rat brains allowed similar levels of engraftment, migration through all hippocampal layers, and considerable proliferation of SVZ-NSCs/SVZ-NSC-derived cells. Differentiation analysis using specific markers demonstrated that SVZ-NSCs differentiated into NeuN mature neurons, GABA-ergic inhibitory interneurons, S-100b+ or GFAP+ astrocytes, NG2+ oligodendrocyte precursors, and Olig2+ oligodendrocyte-like cells at a broadly similar rate in both young and aged rats. This, the authors note, suggests that the hippocampus remains stable with age in relation to its ability to support grafted cells.

Interestingly, the authors also encountered areas in non-neurogenic regions containing doublecortin-positive (DCX+) immature neurons at 3 months, suggesting that the grafted cells retained the ability to establish new neurogenic niches in both young and old animals (See Figure). Further analysis confirmed DCX+ neurons to be newly born neurons derived from engrafted cells and also confirmed the persistence of NSCs within the graft cores.

Good news! It appears that age is not a factor for SVZ-NSC grafts in the hippocampus! While the functional consequences of SVZ-NSC grafting remains to be assessed, this study represents an interesting first step towards the application of cell-based therapies for neurodegenerative disorders/age-related impairments in the elderly population.

References

  1. Shetty AK and Hattiangady B. Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus. Stem Cells Transl Med 2016;5:1204-1215.