Exploring atypical locations of mammalian neural stem cells: the human filum terminale.

Neurogenesis is a multifactorial event determined by local environmental cues, inherent cellular program as well as cellular milieu and may not necessarily be restricted to the SVZ and SGZ. NSCs have been isolated from or neurogenesis has been demonstrated in traditionally non neurogenic regions. This more permissive view of neurogenesis, however, is not widely accepted due to concerns regarding the methodologies used. Furthermore, it is compounded by the fact that the basal levels of increased neurogenesis in such regions has not been completely confirmed and thus precludes a paradigm shift. Were this non limited view of neurogenesis to be generally accepted after thorough investigation, it would open new avenues for regenerative medicine and stem cell therapy.

Transplantation of neural stem cells encapsulated in hydrogels improve functional recovery in a cauda equina lesion model.

This study explored the therapeutic effects of transplantation of neural stem cells (NSCs) encapsulated in hydrogels in a cauda equina lesion model. NSCs were isolated from neonatal dorsal root ganglion (nDRG) and cultured in three-dimensional porous hydrogel scaffolds. Immunohistochemistry, transmission electron microscopy and TUNEL assay were performed to detect the differentiation capability, ultrastructural and pathological changes, and apoptosis of NSCs. Furthermore, the functional recovery of sensorimotor reflexes was determined using the tail-flick test. NSCs derived from DRG were able to proliferate to form neurospheres and mainly differentiate into oligodendrocytes in the three-dimensional hydrogel culture system. After transplantation of NSCs encapsulated in hydrogels, NSCs differentiated into oligodendrocytes, neurons or astrocytes in vivo. Moreover, NSCs engrafted on the hydrogels decreased apoptosis and alleviated the ultrastructural and pathological changes of injured cauda equina. Behavioral analysis showed that transplanted hydrogel-encapsulated NSCs decreased the tail-flick latency and showed a neuroprotective role on injured cauda equina. Our results indicate transplantation of hydrogel-encapsulated NSCs promotes stem cell differentiation into oligodendrocytes, neurons or astrocytes and contributes to the functional recovery of injured cauda equina, suggesting that NSCs encapsulated in hydrogels may be applied for the treatment of cauda equina injury.

Neurochemical architecture of the filum terminale in the rat.

Contrary to the widespread assumption, the filum terminale in the rat possesses a precise glial and neuronal organization. The processes of glial fibrillary acidic protein-stained astrocytes form a rich, three dimensional array. The crescent shaped white matter could be outlined with antibody detecting oligodendrocytes. The neurons in the filum terminale, labeled with neuron-specific nuclear protein, are distributed in a small midline group (dorsal nucleus) dorsal to and in two symmetrical clusters at both sides of the central canal (lateral nuclei). Nitric oxide synthase-, calretinin-, choline acetyltransferase-, substance P- and neurokinin receptor-1-immunoreactive neurons were detected in the lateral nuclei. Axons were classified based on their course and termination. Small number of calcitonin gene-related peptide-immunoreactive fibers was found exclusively in the dorsal nucleus. Nitric oxide synthase-, substance P-, and neurokinin receptor-1-stained axon arborizations were detected mainly in the lateral nucleus. A dense array of extremely fine vesicular glutamate transporter 2- and fine, synaptophysin-immunoreactive varicosities covered densely the lateral nuclei. Fine glycine-transporter 2-immunoreactive axon arborization like structures were seen also in the lateral nucleus. Vesicular glutamate transporter 1- and choline acetyltransferase-immunoreactive axons arborized in the entire gray matter. Serotonin- and enkephalin-immunoreactive fibers congregated in the dorsolateral portion of the white matter, called "shoulder region", while calretinin- and thick, varicose neurokinin receptor-1-stained axons were also seen in the same area of the white matter. Synaptophysin-immunoreactive fine varicosities colocalized only with vesicular glutamate transporter 2 immunoreaction. Substance P and glycine-transporter 2-immunoreactive puncta were found in close contact with neurokinin receptor-1-immunostained perikarya and dendrites.

Acellular Cauda Equina Allograft as Main Material Combined with Biodegradable Chitin Conduit for Regeneration of Long-Distance Sciatic Nerve Defect in Rats.

Autologous nerve grafting (ANG), the gold standard treatment for peripheral nerve defects, still has many restrictions. In this study, the acellular cauda equina allograft (ACEA), which consists of biodegradable chitin conduit and acellular cauda equina, is developed. The cauda equina is able to complete decellularization more quickly and efficiently than sciatic nerves under the same conditions, and it is able to reserve more basal lamina tube. In vitro, ACEA shows superior guidance capacity for the regeneration of axons and migration of Schwann cells compared to acellular sciatic nerve allograft (ASNA) in dorsal root ganglion culture. In vivo, ACEA is used to bridge 15 mm long-distance defects in rat sciatic nerves. On day 21 after transplantation, the regenerative distance of neurofilaments in the grafting segment is not significantly different between the ACEA and ANG groups. At week 12, ACEA group shows better sciatic nerve repair than chitin conduit only and ASNA groups, and the effect is similar to that in the ANG group as determined by gait analysis, neural electrophysiological, and histological analyses. The above results suggest that the ACEA has the potential to become a new biological material as a replacement for autografting in the treatment of long-distance nerve defects.

The brain of the tree pangolin (Manis tricuspis). I. General appearance of the central nervous system.

Here, we describe the superficial appearance of the brain of the rarely studied tree pangolin. Phylogenetic analyses have placed the pangolins, order Pholidota, as a sister group to the order Carnivora. The majority of features visible on the surface of the tree pangolin brain, and its overall appearance can be described as typically mammalian. The pattern of sulci and gyri, while simple, appears very similar to that observed in carnivores. Two derived features of the Pholidota were observed, the first being the rostral decussation of the pyramidal tract, which instead of occurring at the spinomedullary junction, decussates at the level of the caudal pole of the facial nerve nucleus in the rostral medulla oblongata. This appears to be related to the need for voluntary control of the tongue, with a potentially enlarged corticobulbar tract ending in the hypoglossal nucleus. The second derived feature is the very short spinal cord, which terminates midway along the thoracic vertebrae before giving rise to a long and extensive cauda equina. This foreshortened spinal cord appears to be related to anisotropic growth of the somatic and neural elements following early development of the central nervous system. The olfactory system appears to be generally enlarged and is likely the predominant sense used in foraging. Vision and hearing do not appear specialized based on the relative size of the superior and inferior colliculi, but potential somatic specializations indicate that the somatosensory system is heavily relied upon for food consumption and prehensile tail usage.

Characterization of the Filum terminale as a neural progenitor cell niche in both rats and humans.

Neural stem cells (NSCs) reside in a unique microenvironment within the central nervous system (CNS) called the NSC niche. Although they are relatively rare, niches have been previously characterized in both the brain and spinal cord of adult animals. Recently, another potential NSC niche has been identified in the filum terminale (FT), which is a thin band of tissue at the caudal end of the spinal cord. While previous studies have demonstrated that NSCs can be isolated from the FT, the in vivo architecture of this tissue and its relation to other NSC niches in the CNS has not yet been established. In this article we report a histological analysis of the FT NSC niche in postnatal rats and humans. Immunohistochemical characterization reveals that the FT is mitotically active and its cells express similar markers to those in other CNS niches. In addition, the organization of the FT most closely resembles that of the adult spinal cord niche. J. Comp. Neurol. 525:661-675, 2017. © 2016 Wiley Periodicals, Inc.

The Filum Terminale: A Cadaver Study of Anatomy, Histology, and Elastic Properties.

BACKGROUND: The filum terminale is a fibrous band, consisting of the filum terminale internum (FTI), connecting the conus medullaris (CM) with the dural sac (DS), and the filum terminale externum (FTE), connecting the DS with the coccyx. Despite its importance in tethered cord syndrome, published anatomic and physiologic data on the filum terminale remain scarce. We describe 1) the dimensions and position of the FTI and FTE; 2) the histology of the FTI-DS-FTE transition zone; and 3) the extensibility and elastic properties of the FTI and the CM. METHODS: Anatomic measurements were performed on 10 fresh and 10 embalmed human cadavers. Four other fresh cadavers were used for strain and elasticity measurements. RESULTS: The mean FTI and FTE lengths were 158.75 and 69.33 mm, respectively. From cranially to caudally, the FTI diameter decreased from 1.93 to 0.69 mm. The most frequent vertebral level of the CM-FTI and the FTI-DS-FTE junction were L1 and S2, respectively. FTE length correlates with body length (r = 0.54; P = 0.014) and with FTI-DS-FTE junction vertebral level (ρ =-0.76; P < 0.001). Histologically, the FTI fuses with DS fibers and continues as FTE. The FTI and the CM show an exponential loaded weight-strain relationship, with the FTI showing higher strain than the CM and almost perfect elastic properties. The CM strain is increased when the dentate ligaments are cut. CONCLUSIONS: The FTI is an overturned oblate cone-shaped structure, showing bigger strain under weight loading compared with the CM, thereby protecting the CM from traction, together with the dentate ligaments.

The filum terminale externum.

OBJECT: The filum terminale externum (FTE) is the extradural component of the filum terminale internum and little attention has been dedicated to this structure in the literature. The authors theorized that the rare intrasacral ependymomas may originate from ependymal cell collections within the FTE. METHODS: To address this hypothesis, the FTE was dissected and analyzed histologically in 15 adult cadavers. None of the specimens was found to harbor ependymal or other glial cell collections. CONCLUSIONS: The authors found previously undescribed smooth-muscle cells within the FTE. Furthermore, histological analysis identified adipose, nerve, bone, and cartilage cells.

Tapering of human nerve fibres.

To determine the tapering of human nerve fibres, rostral and caudal root pieces of cauda equina nerve roots were removed and nerve fibre diameter distributions were constructed for 4 myelin sheath thickness ranges for the two sites, and compared with each other. The reduction of the group diameter in the different alpha-motoneuron groups was 0.2 % per 13 cm. Accounting for systematic errors, there may be even less tapering. An identified single nerve fibre showed no tapering. Further, there is indication that gamma-motoneurons, preganglionic sympathetic and parasympathetic fibres and skin afferents also reduce their fibre diameter by 0.2 % per 13 cm or less. Consequently, a nerve fibre with a diameter of 10 microm would be reduced to approximately 9.8 microm at 1m from the cell soma. Preganglionic parasympathetic fibres were found to be represented in roots S1 to S5. At similar distances from the spinal cord, the mean diameter of ventral root alpha1-motoneuron (FF) axons increased from the thoracic towards the lumbo-sacral region before decreasing again in the lower sacral region. Usually no alpha1-motoneuron axons were found in S5 roots. The diameter distribution of unmyelinated nerve fibres of a ventral S5 root showed three peaks at 0.25, 0.95 and 1.2 microm. The unmyelinated fibres with diameters around 0.25 microm may represent parasympathetic fibres. In six selected areas of the ventral S5 root, 6.6 times more unmyelinated nerve fibres than myelinated fibres were found on the average.

Organization of the filum terminale in the frog.

The histological organization of the filum terminale of the spinal cord in Rana catesbeiana and Rana pipiens was characterized to determine if this region possessed an organized neuropil or whether it was merely a glial remnant that persisted after absorption of the larval tail. The excised filum was maintained in vitro. Intracellular electrophysiological recording was performed with horseradish peroxidase injection. Tyrosine hydroxylase and serotonin distribution were revealed by immunocytochemical methods. Astroglia were the dominant cell type and displayed an elaborate variety of forms. The mean membrane potential was logarithmically related to the extracellular potassium concentration but displayed a sub-Nernstian slope. Oligodendroglia were also seen, as well as ependyma that extended from the central canal to the pial surface. Neuronal activity was revealed by occasional intracellular penetration of elements that displayed spontaneous excitatory postsynaptic or action potentials. The major evidence for the presence of neurons was the demonstration of tyrosine hydroxylase (TH) immunoreactivity in a large population of cerebrospinal fluid-contacting neurons that abutted the ventral half of the central canal. The axons of these cells entered a ventral bundle and ascended the cord; some fibers left this tract and apparently terminated on large arcuate neurons within the filum. Serotoninergic fibers were primarily confined to a subpial location at the dorsal midline. We conclude that the filum terminale of the frog has a sparse but functional neuropil that is organized around the central canal and supported by a profusion of elaborate glial forms.

Anti-GM1 antibody facilitates leakage in an in vitro blood-nerve barrier model.

Using an in vitro blood-nerve barrier (BNB) model, the authors tested the effect of various monoclonal antiganglioside antibodies on BNB function. Only anti-GM1 antibody significantly facilitated BNB leakage in a concentration-dependent, complement-independent manner. This study provided evidence that anti-GM1 antibody, frequently detected in sera from patients with inflammatory neuropathies, may participate BNB dysfunction and contribute to development of neuropathy.

Incipient cauda equina syndrome as a model of somatovisceral pain in dogs: spinal cord structures involved as revealed by the expression of c-fos and NADPH diaphorase activity.

Segmental and laminar distribution of Fos-like immunoreactive, reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-exhibiting and double-labeled (Fos-like immunoreactive and NADPHd-exhibiting) neurons was examined in lower lumbar and sacral segments of the dog spinal cord using the model of multiple cauda equina constrictions. NADPHd histochemistry was used as marker of nitric oxide synthase-containing neurons. The appearance and the time-course of Fos-like immunoreactive, NADPHd and double-labeled neurons was studied at 2 h and 8 h postconstriction characterized as the incipient phase of cauda equina syndrome. The occurrence of Fos-like immunoreactive and NADPHd-exhibiting neurons in fully developed cauda equina syndrome was studied at five days postconstriction. An increase in Fos-like immunoreactivity in superficial laminae (I-II) and an enhanced NADPHd staining of lamina VIII neurons were found. A statistically significant increase in Fos-like immunoreactive neurons was found in laminae I-II and VIII-X 8 h postconstriction, and in contrast, a prominent decrease in Fos-like immunoreactive neurons was found in laminae I-II, accompanied by a statistically significant increase in Fos-like immunoreactive neurons in more ventrally located laminae VII-X at five days postconstriction. Quantitative analysis of laminar distribution of constriction-induced NADPHd-exhibiting neurons revealed a considerable increase in these neurons in laminae VIII-IX 8 h postconstriction and a statistically highly significant increase in NADPHd-exhibiting neurons in laminae VII-X five days postconstriction. Concurrently, the number of NADPHd-exhibiting neurons in laminae I-II was greatly reduced. While a low number of double-labeled neurons was found throughout the gray matter of lower lumbar and sacral segments at 2 h postconstriction, a statistically significant number of double-labeled neurons was found in lamina X 8 h and in laminae VII-X five days postconstriction. The course and distribution of anterograde degeneration resulting five days after multiple cauda equina constrictions are compared with segmental and laminar distribution of Fos-like immunoreactive and NADPHd-exhibiting neurons. Prominent involvement of the spinal cord neurons appearing in the lumbosacral segments at the early beginning and in fully developed cauda equina syndrome results in a Fos-like immunoreactivity and strongly enhanced NADPHd staining of some neuronal pools. Under such circumstances, an early cauda equina decompression surgery is advisable aimed at decreasing or preventing the derangement of the neural circuits in the lumbosacral segments.

The ventriculus terminalis and filum terminale of the human spinal cord.

Serial sections of the conus medullaris and the filum terminale of 23 randomly selected human spinal cords were studied by light and electron microscopy, and following immunoperoxidase staining for glial fibrillary acidic protein (GFAP), vimentin, neuron-specific enolase (NSE), amyloid beta protein, and S-100 protein. The intradural portion of the filum contains bundles of GFAP-positive glial fibers, scattered silver- and NSE-positive neurons, segments of peripheral nerve, blood vessels, fibrous connective tissue, and fat. Glial cell clusters varying from five to 100 cell layers thick at times constitute the bulk of the filum. The periependymal glial cells possess moderate amounts of eosinophilic cytoplasm and relatively uniform round to ovoid nuclei containing evenly distributed chromatin. They are distributed diffusely with no specific pattern of organization, although some of them showed a tendency to form acinar structures. A minority of the glial cells showed GFAP immunoreactivity, and some were immunoreactive for vimentin. Electron microscopy demonstrated the presence of periependymal cells showing cilia, microvilli, and the formation of intercellular junctional complexes, as well as cells containing bundles of glial filaments within the cytoplasm. Degenerated NSE-positive neurons and degenerated neurites resembling neuritic plaques were also demonstrated. However, immunoperoxidase staining for amyloid beta protein was negative in these structures. Thus, the filum terminale is endowed with an abundance of glial cells and neurons and is not simply a fibrovascular tag. Periependymal glial cells in the filum terminale should not be mistaken for neoplasm. The presence of neuropil with profuse astroglial and neuronal components within the filum terminale suggests a possible functional role for these structures.

Membrane currents and morphological properties of neurons and glial cells in the spinal cord and filum terminale of the frog.

Using the patch-clamp technique in the whole-cell configuration combined with intracellular dialysis of the fluorescent dye Lucifer yellow (LY), the membrane properties of cells in slices of the lumbar portion of the frog spinal cord (n=64) and the filum terminale (FT, n=48) have been characterized and correlated with their morphology. Four types of cells were found in lumbar spinal cord and FT with membrane and morphological properties similar to those of cells that were previously identified in the rat spinal cord (Chvátal, A., Pastor, A., Mauch, M., Syková, E., Kettenmann, H., 1995. Distinct populations of identified glial cells in the developing rat spinal cord: Ion channel properties and cell morphology. Eur. J. Neurosci. 7, 129-142). Neurons, in response to a series of symmetrical voltage steps, displayed large repetitive voltage-dependent Na(+) inward currents and K(+) delayed rectifying outward currents. Three distinct types of non-neuronal cells were found. First, cells that exhibited passive symmetrical non-decaying currents were identified as astrocytes. These cells immunostained for GFAP and typically had at least one thick process and a number of fine processes. Second, cells with the characteristic properties of rat spinal cord oligodendrocytes, with passive symmetrical decaying currents and large tail currents after the end of the voltage step. These cells exhibited either long parallel or short hairy processes. Third, cells that expressed small brief inward currents in response to depolarizing steps, delayed rectifier outward currents and small sustained inward currents identical to rat glial precursor cells. Morphologically, they were characterized by round cell bodies with a number of finely branched processes. LY dye-coupling in the frog spinal cord gray matter and FT was observed in neurons and in all glial populations. All four cell types were found in both the spinal cord gray matter and FT. The glia/neuron ratio in the spinal cord was 0.78, while in FT it was 2.0. Moreover, the overall cell density was less in the FT than in the spinal cord. The present study shows that the membrane and morphological properties of glial cells in the frog and rat spinal cords are similar. Such striking phylogenetic similarity suggests a significant contribution from distinct glial cell populations to various spinal cord functions, particularly ionic and volume homeostasis in both mammals and amphibians.

Development of the posterior neural tube in human embryos.

Development of the posterior neural tube (PNT) in human embryos is a complicated process that involves both primary and secondary neurulation. Because normal development of the PNT is not fully understood, pathogenesis of spinal neural tube defects remains elusive. To clarify the mechanism of PNT development, we histologically examined 20 human embryos around the stage of posterior neuropore closure and found that the developing PNT can be divided into three parts: 1) the most rostral region, which corresponds to the posterior part of the primary neural tube, 2) the junctional region of the primary and secondary neural tubes, and 3) the caudal region, which emerges from the neural cord. In the junctional region, the axially-condensed mesenchyme (AM) intervened between the neural plate/tube and the notochord at the stage of posterior neuropore closure, while the notochord was directly attached to the neural plate/tube in the most rostral region. A single cavity was found to be formed in the AM as the presumptive luminal surface cells were radially aligned in the junctional region prior to the formation of the neural cord. The single cavity was continuous with the central cavity of the primary neural tube. In contrast, multiple or isolated cavities were frequently observed in the caudal region of the PNT. Our observation suggests that the junctional region of the PNT is distinct from other regions in terms of the relationship with the notochord and the mode of cavitation during secondary neurulation.

Ependymal cells variations in the central canal of the rat spinal cord filum terminale: an ultrastructural investigation.

OBJECTIVE: The ependymal cells, considered today as an active participant in neuroendocrine functions, were investigated by electron microscopy in the central canal of the lowest spinal cord, the filum terminale (FT), in adult rats. In this area of the spinal cord, the central canal is covered by a heterogeneous population of ependymal cells. The aim of the present work was to compare the regional features of the ependymal cells in two different parts of the FT with a special regard to their ultrastructure. METHODS: Two parts of the FT were selected for the ultrastructural observations: the rostral (rFT) and the caudal (cFT) ones. The rTF was removed at the level of the immediate continuation of the conus medullaris, while the cFT 30 mm further caudally. After formaldehyde fixation, the spinal cord was removed and cut into small blocks for electron microscopic processing. The material was embedded into durcupan, contrasted with uranyl acetate, lead citrate as well as osmium tetroxide, and investigated under JEOL 1200 EX electron microscope. RESULTS: In the rFT, the ependymal lining is pseudostratified and one-layered in the cFT, whereas the shape of the ependymal cells may vary from cuboidal to flatten in the rostro-caudal direction. The basal membrane of many ependymal cells possesses deep invaginations, so called "filum terminale labyrinths". Many neuronal processes occur in the pericanalicular neuropil. In contrast to the rFT, the cFT is less rich in the neuropil particles. Some of the ependymal cells concurrently reach both the intracanalicular and extracanalicular cerebrospinal fluid (CSF), thus they may represent a new variant of the ependymal cells designated as "bridge cells of the FT". CONCLUSIONS: The present data indicate that the FT ependymal cells exhibit clear differences in anatomy as well as ultrastructure that may reflect their distinct functional activity. Therefore, observations presented here may serve for the better understanding of the physiological role of the individual ependymal areas in this special portion of the rat spinal cord.

The postnatal human filum terminale is a source of autologous multipotent neurospheres capable of generating motor neurons.

BACKGROUND: Neural progenitor cells (NPCs) are undifferentiated and mitotic and can be induced to differentiate into neurons and glia, the building blocks of the nervous system. NPCs have great therapeutic potential for nervous system trauma and degenerative disorders. They have been identified in the mammalian central nervous system, but current sources are difficult to access surgically and come from regions that are critical for normal brain function. OBJECTIVE: To identify and characterize in detail a novel source of human NPCs in the filum terminale (FT), a vestigial structure at the caudal end of the spinal cord, which is easily accessed and plays no functional role in the postnatal nervous system. METHODS: Cells were isolated and cultured in vitro from the FT of terminated fetuses and from children and adolescents who had undergone surgical resections for tethered spinal cords. Cell culture techniques, immunohistochemistry, and immunocytochemistry were applied to examine FT cells. RESULTS: : FT cells gave rise to neurospheres that proliferated over extended periods of time in culture. These neurospheres were positive for neural stem/progenitor cell markers by immunocytochemical staining. The neurospheres were able to be induced to differentiate in vitro into neurons and glial cells, which were confirmed by the use of antibodies against the cell type-specific markers. Moreover, they have been induced to form motor neurons capable of innervating striated muscle in vitro. CONCLUSION: Multipotent NPC cells from the FT are both accessible and expendable. They may allow autologous cell-based transplantation therapy that circumvents immunological rejection.

The isolation, differentiation, and survival in vivo of multipotent cells from the postnatal rat filum terminale.

Neural stem cells (NSCs) are undifferentiated cells in the central nervous system (CNS) that are capable of self-renewal and can be induced to differentiate into neurons and glia. Current sources of mammalian NSCs are confined to regions of the CNS that are critical to normal function and surgically difficult to access, which limits their therapeutic potential in human disease. We have found that the filum terminale (FT), a previously unexplored, expendable, and easily accessible tissue at the caudal end of the spinal cord, is a source of multipotent cells in postnatal rats and humans. In this study, we used a rat model to isolate and characterize the potential of these cells. Neurospheres derived from the rat FT are amenable to in vitro expansion in the presence of a combination of growth factors. These proliferating, FT-derived cells formed neurospheres that could be induced to differentiate into neural progenitor cells, neurons, astrocytes, and oligodendrocytes by exposure to serum and/or adhesive substrates. Through directed differentiation using sonic hedgehog and retinoic acid in combination with various neurotrophic factors, FT-derived neurospheres generated motor neurons that were capable of forming neuromuscular junctions in vitro. In addition, FT-derived progenitors that were injected into chick embryos survived and could differentiate into both neurons and glia in vivo.

Distribution and characterization of progenitor cells within the human filum terminale.

BACKGROUND: Filum terminale (FT) is a structure that is intimately associated with conus medullaris, the most caudal part of the spinal cord. It is well documented that certain regions of the adult human central nervous system contains undifferentiated, progenitor cells or multipotent precursors. The primary objective of this study was to describe the distribution and progenitor features of this cell population in humans, and to confirm their ability to differentiate within the neuroectodermal lineage. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that neural stem/progenitor cells are present in FT obtained from patients treated for tethered cord. When human or rat FT-derived cells were cultured in defined medium, they proliferated and formed neurospheres in 13 out of 21 individuals. Cells expressing Sox2 and Musashi-1 were found to outline the central canal, and also to be distributed in islets throughout the whole FT. Following plating, the cells developed antigen profiles characteristic of astrocytes (GFAP) and neurons (ß-III-tubulin). Addition of PDGF-BB directed the cells towards a neuronal fate. Moreover, the cells obtained from young donors shows higher capacity for proliferation and are easier to expand than cells derived from older donors. CONCLUSION/SIGNIFICANCE: The identification of bona fide neural progenitor cells in FT suggests a possible role for progenitor cells in this extension of conus medullaris and may provide an additional source of such cells for possible therapeutic purposes. Filum terminale, human, progenitor cells, neuron, astrocytes, spinal cord.