Source Of Neural Stem Cells Research Articles

Nestin-positive cells in the spinal cord: a potential source of neural stem cells

Some literatures have reported neural precursor cells (NPCs) exist in spinal cord of adult mammal, however, the NPCs distribution feature in spinal cord of adult mice so far is not described in detail. In order to observe and compare the distribution feature of NPCs in various spinal cord regions of adult mice, to research a potential source of neural stem cells (NSCs), we obtained NPCs distribution feature by analyzing the distribution of the nestin-containing cells (NCCs) in spinal cord of adult nestin second-intron enhancer controlled LacZ reporter transgenic mice (pNes-Tg) with LacZ staining and positive cell quantification. The results showed that: NCCs were observed in various regions of spinal cord of adult mice, but amount of NCCs was different in distinct region, the rank order of NCCs amount in various spinal cord regions was dorsal horn region greater than central canal greater than the ventral and lateral horn. NCCs in dorsal horn region mainly distributed in substantia gelatinosa, NCCs in central canal mainly distributed in ependymal zone, on the contrary, NCCs in ventral, lateral horn, medullae, nucleus regions of spinal cord were comparatively less. The rank order of NCCs amount in various spinal cord segments was cervical segment greater than lumbar sacral segment greater than thoracic segment. There was no significantly difference between NCCs amount in the left and right sides, and within cervical 1–7, thoracic 1–12, lumbar 1–5, sacral segment of spinal cord in adult mice. These data collectively indicate that NPCs extensively distribute in various regions of spinal cord of adult mice, especially in substantia gelatinosa and ependymal zone. NPCs in cervical segment are abundant, NPCs in thoracic segment are the least while compared the different spinal cord segment, the NPCs in various regions of spinal cord of adult mice are a potential source of NSCs.

Human fetal cortical and striatal neural stem cells generate region‐specific neurons in vitro and differentiate extensively to neurons after intrastriatal transplantation in neonatal rats

Human fetal brain is a potential source of neural stem cells (NSCs) for cell replacement therapy in neurodegenerative diseases. We explored whether NSCs isolated from cortex and striatum of human fetuses, aged 6-9 weeks post-conception, maintain their regional identity and differentiate into specific neuron types in culture and after intrastriatal transplantation in neonatal rats. We observed no differences between cortex- and striatum-derived NSCs expanded as neurospheres in proliferative capacity, growth rate, secondary sphere formation, and expression of neural markers. After 4 weeks of differentiation in vitro, cortical and striatal NSCs gave rise to similar numbers of GABAergic and VMAT2- and parvalbumin-containing neurons. However, whereas cortical NSCs produced higher number of glutamatergic and tyrosine hydroxylase- and calretinin-positive neurons, several-fold more neurons expressing the striatal projection neuron marker, DARPP-32, were observed in cultures of striatal NSCs. Human cortical and striatal NSCs survived and migrated equally well after transplantation. The two NSC types also generated similar numbers of mature NeuN-positive neurons, which were several-fold higher at 4 months as compared to at 1 month after grafting. At 4 months, the grafts contained cells with morphologic characteristics of neurons, astrocytes, and oligodendrocytes. Many of neurons were expressing parvalbumin. Our data show that NSCs derived from human fetal cortex and striatum exhibit region-specific differentiation in vitro, and survive, migrate, and form mature neurons to the same extent after intrastriatal transplantation in newborn rats.

Neural stem cells for the treatment of disorders of the enteric nervous system: Strategies and challenges

The main goal of this review is to summarize the status of the research in the field of stem cells transplantation, as it is applicable to the treatment of gastrointestinal motility. This field of research has advanced tremendously in the past 10 years, and recent data produced in our laboratories as well as others is contributing to the excitement on the use of neural stem cells (NSC) as a valuable therapeutic approach for disorders of the enteric nervous system characterized by a loss of critical neuronal subpopulations. There are several sources of NSC, and here we describe therapeutic strategies for NSC transplantation in the gut. These include using NSC as a relatively nonspecific cellular replacement strategy in conditions where large populations of neurons or their subsets are missing or destroyed. As with many other recent "breakthroughs" stem cell therapy may eventually prove to be overrated. However, at the present time, it does appear to provide the hope for a true cure for many currently intractable diseases of both the central and the peripheral nervous system. Certainly more extensive research is needed in this field. We hope that our review will encourage new investigators in entering this field of research ad contribute to our knowledge of the potentials of NSC and other cells for the treatment of gastrointestinal dysmotility.

Cellule Staminali per le malattie neurodegenerative: quali fonti e quali obiettivi?

Since their identification Neural Stem Cells (NSCs) have been considered an attractive subject for therapeutic applications to the damaged brain. However, toward such a goal and in spite of the excitement, a great deal of basic research is still needed since thein vitro properties of these cells remain poorly understood and theirin vivo engraftment capacity is of limited efficacy. NSCs derived from fetal and adult neural tissue are actually expanded as cell aggregates, named neurospheres, that grow in suspension. Neurospheres have been shown capable to differentiatein vitro to astrocytes and neurons, even after several passages but are, however, composed by a heterogeneous population of cells at different maturation stages. At the state of the art, an important requirement is for procedures that allow consistent and more uniform neuronal differentiation of the neurospheres cells after intracerebral transplantation. Outside the CNS, another potential source of NSC is the blastocyst, from which rodent and human ES cells have been derived. NSCs have been efficiently derived from ES cells and their potential has been tested bothin vitro andin vivo. Beside the promises offered by the ES cell-derived and adult NSCs, the data available demonstrate that NSCs implanted into the adult or developing brain generate mostly glial cells, suggesting that the control on the differentiative fate remains the main open question. In this context it will be important to understand the real impact of adult mammalian neurogenesis and to investigate more deeply how the environment may be exploited to favour the integration and the survival of cells in the diseased brain. The future development of strategies and the exploitation of target molecules able to improve the rate of neuronal, over glial, differentiation and survival by genetically engineering NSC represents the major challenge in the field. This approach coupled to a range of pharmacological approaches and therapeutic strategies to efficiently recruit endogenous or exogenous NSCs clearly represent one of the most important future challenges for basic and clinical research.

Neural regeneration in the chick retina

In warm-blooded vertebrates, possibilities for retinal regeneration have recently become reality with the discovery of neural stem cells in the mature eye. A number of different cellular sources of neural stem cells have been identified. These sources include stem cells at the retinal margin, pigmented cells in the ciliary body and iris, non-pigmented cells in the ciliary body and Müller glia within the retina. This review focuses on recent reports of neural stem cells and regeneration in the postnatal chicken retina. In the chicken eye sources of neurogensis and regeneration include: (1) retinal stem cells at the peripheral edge of the retina; (2) Müller glia in central regions of the retina; (3) non-pigmented epithelial cells in the posterior portion of the ciliary body; and (4) possibly pigmented cells in the pars plana of the ciliary body. This review discusses the similarities between the retinal progenitor cells in the postnatal eye and those found in the embryo. In addition, I discuss combinations of growth factors, (insulin, IGF-I, EGF and FGF2) that are capable of stimulating the proliferation and production of neurons from neural progenitors, non-neural epithelial cells, and postmitotic support cells in the avian eye. In summary, the mechanisms that regulate the proliferation and differentiation of cells with neurogenic potential are beginning to be understood and the postnatal chicken eye has proven to be a useful model system to study retinal regeneration.

Evidence of newly generated neurons in the human olfactory bulb

The subventricular zone (SVZ) is known to be the major source of neural stem cells in the adult brain. In rodents and nonhuman primates, many neuroblasts generated in the SVZ migrate in chains along the rostral migratory stream (RMS) to populate the olfactory bulb (OB) with new granular and periglomerular interneurons. In order to know if such a phenomenon exists in the adult human brain, we applied single and double immunostaining procedures to olfactory bulbs obtained following brain necropsy in normal adult human subjects. Double immunofluorescence labelling with a confocal microscope served to visualize cells that express markers of proliferation and immature neuronal state as well as markers that are specific to olfactory interneurons. Newborn cells that express cell cycle proteins [Ki-67, proliferating cell nuclear antigen (PCNA)] were detected in the granular and glomerular layers (GLs) of the human olfactory bulb; these cells coexpressed markers of immature neuronal state, such as Doublecortin (DCX), NeuroD and Nestin. Numerous differentiating cells expressed molecular markers of early committed neurons [β-tubulin class III (TuJ1)] and were also immunoreactive for glutamic acid decarboxylase (GAD), a marker of GABAergic neurons, or tyrosine hydroxylase (TH), a marker of dopaminergic neurons. Other early committed neurons expressed the calcium-binding proteins calretinin (CR) or parvalbumin (PV). These results provide strong evidence for the existence of adult neurogenesis in the human olfactory system. Despite its relatively small size compared to that in rodents and nonhuman primates, the olfactory bulb in humans appears to be populated, throughout life, by new granular and periglomerular neurons that express a wide variety of chemical phenotypes.

Adult neural stem cells from the mouse subventricular zone are limited in migratory ability compared to progenitor cells of similar origin

The subventricular zone (SVZ) in the forebrain is the largest source of neural stem cells and progenitor cells in the adult CNS. To assess the ability of adult neural stem cells to survive, differentiate and migrate, we have compared the behavior of dissociated, neurosphere-derived stem cells with that of progenitor cells in transplantation experiments. This ability was first tested in vivo, offering the stem cells the possibility to migrate along the rostral migratory stream (RMS), their specific pathway. In addition, the differential behaviors of the two classes of cells were also compared in vitro by grafting them into organotypic slice cultures containing either tangential (embryonic cerebral cortex) or radial (early postnatal cerebellar cortex) migratory routes. Most of the grafted adult neurosphere-derived stem cells survived and integrated in vivo, and a proportion of them differentiate into neurons, oligodendrocytes or astrocytes. However, they were unable to migrate along the RMS and remained in the vicinity of the injection site. In contrast, SVZ progenitor cells were able to migrate toward the olfactory bulb and, once there, to acquire the phenotype of granule cells, as previously reported. In vitro, neural stem cells exhibited a better migratory ability, although they only migrated for short distances, particularly, in forebrain slices. Nevertheless, the average distance covered by progenitor cells was a two-fold longer than that covered by neural stem cells, corroborating that this class of more specified cells has higher migratory ability. These results suggest that the in vitro conditions of expanding SVZ-derived stem cells, required to maintain them in an immature stage might modify their intrinsic properties, preventing their differentiation into neuroblasts and their subsequent migration.

Neural Stem Cells for Neurological Disorders

Recent progress shows that neurons suitable for transplantation can be generated from neural stem cells (NSCs) in culture, and that the adult brain produces new neurons from its own stem cells in response to injury. In this article, we discuss how the subventricular zone of the forebrain is the most active neurogenetic area and the richest source of NSCs. This review also focuses on the nature and functional properties of NSCs of the adult mammalian brain, and we propose our views on the strategy from bench to the clinic with particular concerns and considerations.

Neural stem cells: an overview.

This review focuses on the nature and functional properties of stem cells of the adult mammalian central nervous system (CNS). It has recently been shown that cell turnover, including neurons, does occur in the mature CNS, thanks to the persistence of precursor cells that possess the functional characteristics of bona-fide neural stem cells (NSCs) within restricted brain areas. We discuss how the subventricular zone of the forebrain (SVZ) is the most active neurogenetic area and the richest source of NSCs. These NSCs ensure a life-long contribution of new neurons to the olfactory bulb and, when placed in culture, can be grown and extensively expanded for months, allowing the generation of stem cell lines, which maintain stable and constant functional properties. A survey of the differentiation potential of these NSCs, both in vitro and in vivo, outlines their extreme plasticity that seems to outstretch the brain boundaries, so that these neuroectodermal stem cells may give rise to cells that derive from developmentally distinct tissues. A critical discussion of the latest, controversial findings regarding this surprising phenomenon is provided.

Large-scale sources of neural stem cells.

Large-scale sources of neural stem cells are crucial for both basic research and novel approaches toward treating neurological disorders. Three sources that produce neural cells closely resembling their normal counterparts are now available: oncogene immortalized stem cells, neurospheres, and embryonic stem cell (ES)-derived neural cells. Cells including multiple subtypes of CNS and PNS neurons, as well as oligodendrocytes, Schwann cells, and astrocytes, are modeled by these large-scale sources. Although most cell lines were originally from rodents, their human counterparts are being discovered and characterized.

Neural stem cells in the adult mammalian forebrain: A relatively quiescent subpopulation of subependymal cells

Dissection of the subependyma from the lateral ventricle of the adult mouse forebrain is necessary and sufficient for the in vitro formation of clonally derived spheres of cells that exhibit stem cell properties such as self-maintenance and the generation of a large number of progeny comprising the major cell types found in the central nervous system. Killing the constitutively proliferating cells of the subependyma in vivo has no effect on the number of stem cells isolated in vitro and induces a complete repopulation of the subependyma in vivo by relatively quiescent stem cells found within the subependyma. Depleting the relatively quiescent cell population within the subependyma in vivo results in a corresponding decrease in spheres formed in vitro and in the final number of constitutively proliferating cells in vivo, suggesting that a relatively quiescent subependymal cell is the in vivo source of neural stem cells.