Search results for "Neural stem cell"
showing 10 items of 250 documents
Prox1 Is Required for Oligodendrocyte Cell Identity in Adult Neural Stem Cells of the Subventricular Zone
2016
Abstract Adult neural stem cells with the ability to generate neurons and glia cells are active throughout life in both the dentate gyrus (DG) and the subventricular zone (SVZ). Differentiation of adult neural stem cells is induced by cell fate determinants like the transcription factor Prox1. Evidence has been provided for a function of Prox1 as an inducer of neuronal differentiation within the DG. We now show that within the SVZ Prox1 induces differentiation into oligodendrocytes. Moreover, we find that loss of Prox1 expression in vivo reduces cell migration into the corpus callosum, where the few Prox1 deficient SVZ-derived remaining cells fail to differentiate into oligodendrocytes. Thu…
Positive Controls in Adults and Children Support That Very Few, If Any, New Neurons Are Born in the Adult Human Hippocampus.
2020
Adult hippocampal neurogenesis was originally discovered in rodents. Subsequent studies identified the adult neural stem cells and found important links between adult neurogenesis and plasticity, behavior, and disease. However, whether new neurons are produced in the human dentate gyrus (DG) during healthy aging is still debated. We and others readily observe proliferating neural progenitors in the infant hippocampus near immature cells expressing doublecortin (DCX), but the number of such cells decreases in children and few, if any, are present in adults. Recent investigations using dual antigen retrieval find many cells stained by DCX antibodies in adult human DG. This has been interprete…
Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.
2018
New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus(1-5). This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease(6-10). In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day(11), whereas other studies find many fewer putative new neurons(12-14). Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal …
Adult rat myelin enhances axonal outgrowth from neural stem cells.
2018
Axon regeneration after spinal cord injury (SCI) is attenuated by growth inhibitory molecules associated with myelin. We report that rat myelin stimulated the growth of axons emerging from rat neural progenitor cells (NPCs) transplanted into sites of SCI in adult rat recipients. When plated on a myelin substrate, neurite outgrowth from rat NPCs and from human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) was enhanced threefold. In vivo, rat NPCs and human iPSC-derived NSCs extended greater numbers of axons through adult central nervous system white matter than through gray matter and preferentially associated with rat host myelin. Mechanistic investigations excluded …
Intraspinal stem cell transplantation for amyotrophic lateral sclerosis: Ready for efficacy clinical trials?
2016
Intraspinal stem cell (SC) transplantation represents a new therapeutic approach for amyotrophic lateral sclerosis (ALS) clinical trials. There are considerable difficulties in designing future efficacy trials, some related to the field of ALS and some that are specific to SCs or the mode of delivery. In October 2015, the most controversial points on SC transplantation were addressed during an international workshop intended to bring together international SC and ALS researchers in a public discussion on a topic for which expertise is limited. During the meeting, a discussion was started on the basic structure of the ideal clinical trial testing the efficacy and safety of SC transplantation…
Corrigendum: Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine mod…
2017
Current treatments for demyelinating diseases are generally only capable of ameliorating the symptoms, with little to no effect in decreasing myelin loss nor promoting functional recovery. Mesenchymal stem cells (MSCs) have been shown by many researchers to be a potential therapeutic tool in treating various neurodegenerative diseases, including demyelinating disorders. However, in the majority of the cases, the effect was only observed locally, in the area surrounding the graft. Thus, in order to achieve general remyelination in various brain structures simultaneously, bone marrow-derived MSCs were transplanted into the lateral ventricles (LVs) of the cuprizone murine model. In this manner…
Isolation, culture and analysis of adult subependymal neural stem cells
2016
Individual cells dissected from the subependymal neurogenic niche of the adult mouse brain proliferate in medium containing basic fibroblast growth factor (bFGF) and/or epidermal growth factor (EGF) as mitogens, to produce multipotent clonal aggregates called neurospheres. These cultures constitute a powerful tool for the study of neural stem cells (NSCs) provided that they allow the analysis of their features and potential capacity in a controlled environment that can be modulated and monitored more accurately than in vivo. Clonogenic and population analyses under mitogen addition or withdrawal allow the quantification of the self-renewing and multilineage potency of these cells and the id…
Conversion of Nonproliferating Astrocytes into Neurogenic Neural Stem Cells: Control by FGF2 and Interferon-gamma
2016
Abstract Conversion of astrocytes to neurons, via de-differentiation to neural stem cells (NSC), may be a new approach to treat neurodegenerative diseases and brain injuries. The signaling factors affecting such a cell conversion are poorly understood, and they are hard to identify in complex disease models or conventional cell cultures. To address this question, we developed a serum-free, strictly controlled culture system of pure and homogeneous “astrocytes generated from murine embryonic stem cells (ESC).” These stem cell derived astrocytes (mAGES), as well as standard primary astrocytes resumed proliferation upon addition of FGF. The signaling of FGF receptor tyrosine kinase converted G…
Increasing Neural Stem Cell Division Asymmetry and Quiescence Are Predicted to Contribute to the Age-Related Decline in Neurogenesis.
2018
Summary: Adult murine neural stem cells (NSCs) generate neurons in drastically declining numbers with age. How cellular dynamics sustain neurogenesis and how alterations with age may result in this decline are unresolved issues. We therefore clonally traced NSC lineages using confetti reporters in young and middle-aged adult mice. To understand the underlying mechanisms, we derived mathematical models that explain observed clonal cell type abundances. The best models consistently show self-renewal of transit-amplifying progenitors and rapid neuroblast cell cycle exit. In middle-aged mice, we identified an increased probability of asymmetric stem cell divisions at the expense of symmetric di…
Taking Advantage of Nature’s Gift: Can Endogenous Neural Stem Cells Improve Myelin Regeneration?
2016
Irreversible functional deficits in multiple sclerosis (MS) are directly correlated to axonal damage and loss. Neurodegeneration results from immune-mediated destruction of myelin sheaths and subsequent axonal demyelination. Importantly, oligodendrocytes, the myelinating glial cells of the central nervous system, can be replaced to some extent to generate new myelin sheaths. This endogenous regeneration capacity has so far mainly been attributed to the activation and recruitment of resident oligodendroglial precursor cells. As this self-repair process is limited and increasingly fails while MS progresses, much interest has evolved regarding the development of remyelination-promoting strateg…