Source Of Neural Stem Cells Research Articles

Use of Immunocytochemical Methods to Identify the Boundaries between the Subventricular Zone of the Telencephalon and the Striatum

The subventricular zone (SVZ) of the telencephalon, which is the main source of neural stem cells in adult mammals, is poorly defined using standard histological stains. We report here our studies on the possibility of using immunochemical approaches for the clear identification of the boundaries between the SVZ and the striatum. Use of reactions for tyrosine hydroxylase and synaptophysin was found to be optimum in terms of defining the boundaries between the striatum and the SVZ in different mammals.

Stem Cell-Based Therapy in Neural Repair

Cell-based therapy could aid in alleviating symptoms or even reversing the progression of neurodegenerative diseases and nerve injuries. Fibroblast growth factor 1 (FGF1) has been shown to maintain the survival of neurons and induce neurite outgrowth. Accumulating evidence suggests that combination of FGF1 and cell-based therapy is promising for future therapeutic application. Neural stem cells (NSCs), with the characteristics of self-renewal and multipotency, can be isolated from embryonic stem cells, embryonic ectoderm, and developing or adult brain tissues. For NSC clinical application, several critical problems remain to be resolved: (1) the source of NSCs should be personalized; (2) the isolation methods and protocols of human NSCs should be standardized; (3) the clinical efficacy of NSC transplants must be evaluated in more adequate animal models; and (4) the mechanism of intrinsic brain repair needs to be better characterized. In addition, the ideal imaging technique for tracking NSCs would be safe and yield high temporal and spatial resolution, good sensitivity and specificity. Here, we discuss recent progress and future development of cell-based therapy, such as NSCs, induced pluripotent stem cells, and induced neurons, in neurodegenerative diseases and peripheral nerve injuries.

Symmetric Expansion of Neural Stem Cells from the Adult Olfactory Bulb Is Driven by Astrocytes Via WNT7A

Adult neural stem cells (NSCs) located in the subventricular zone (SVZ) persistently produce new neurons destined to the olfactory bulb (OB). Recent research suggests that the OB is also a source of NSCs that remains largely unexplored. Using single/dual-labeling procedures, we address the existence of NSCs in the innermost layers of the OB. In vivo, these cells are more quiescent that their SVZ counterparts, but after in vitro expansion, they behave similarly. Self-renewal and proliferation assays in co-culture with niche astrocytes indicate that OB-glia restricts NSC activity whereas SVZ-glia has the opposite effect. Gene expression profiling identifies WNT7A as a key SVZ-glial factor lacking in OB-glia that enhances self-renewal, thereby improving the propagation of OB-NSC cultures. These data demonstrate that region-specific glial factors account for in vivo differences in NSC activity and point to WNT7A as a tool that may be instrumental for the NSC expansion phase that precedes grafting.

The Amniotic Fluid As a Source of Neural Stem Cells in the Setting of Experimental Neural Tube Defects

We sought to determine whether neural stem cells (NSCs) can be isolated from the amniotic fluid in the setting of neural tube defects (NTDs), as a prerequisite for eventual autologous perinatal therapies. Pregnant Sprague-Dawley dams (n=62) were divided into experimental (n=42) and control (n=20) groups, depending on prenatal exposure to retinoic acid for the induction of fetal NTDs. Animals were killed before term for analysis (n=685 fetuses). Amniotic fluid samples from both groups underwent epigenetic selection for NSCs, followed by exposure to neural differentiation media. Representative cell samples underwent multiple morphological and phenotypical analyses at different time points. No control fetus (n=267) had any structural abnormality, whereas at least one type of NTD developed in 52% (217/418) of the experimental fetuses (namely, isolated spina bifida, n=144; isolated exencephaly, n=24; or a combination of the two, n=49). Only amniotic samples from fetuses with a NTD yielded cells with typical neural progenitor morphology and robust expression of both Nestin and Sox-2, primary markers of NSCs. These cells responded to differentiation media by displaying typical morphological changes, along with expression of beta-tubulin III, glial fibrillary acidic protein, and/or O4, markers for immature neurons, astrocytes, and oligodendrocytes, respectively. This was concurrent with downregulation of Nestin and Sox-2. We conclude that the amniotic fluid can harbor disease-specific stem cells, for example, NSCs in the setting of experimental NTDs. The amniotic fluid may be a practical source of autologous NSCs applicable to novel forms of therapies for spina bifida.

Neural progenitor cells derived from adult bone marrow mesenchymal stem cells promote neuronal regeneration

AimIt is well known that neural stem/progenitor cells (NS/PC) are an ideal cell type for the treatment of central nervous system (CNS) disease. However, ethical problems have severely hampered fetal NS/PC from being widely used as a source for stem cell therapy. Recently, it has been demonstrated that autologous bone marrow mesenchymal stem cells (BMSC) can transdifferentiate into neural progenitor cells (NPC). The biological function of BMSC derived NPC (MDNPC) in neuronal systems remains unknown. In the present study, we aimed to investigate whether MDNPC can promote in vitro neural regeneration, a process comprising mainly the generation of neurons and neurotransmitters. Main methodsWe co-cultured BMSC, MDNPC or fetal NS/PC with PC12 cells and studied their roles on proliferation, neurite formation and dopamine release from PC12 cells. Furthermore, we also explored the mechanisms by which MDNPC regulate dopamine secretion from PC12 derived neural cells using Western blot. Key findingsWe found that both MDNPC and NS/PC had similar morphologies and there were no significant differences between MDNPC and NS/PC in promoting PC12 cell proliferation, neurite outgrowth, and dopamine release. We also demonstrated that NS/PC induced dopamine secretion was associated with an upregulation of dopamine transporter (DAT) levels. SignificanceIn summary, MDNPC were comparable to NS/PC in promoting neural regeneration, indicating that MDNPC are a promising candidate source of neural stem cells for the treatment of neurological diseases.

Regional differences of proliferation activity in the spinal cord ependyma of adult rats

Abstract Increased proliferation activity in the central canal ependyma of adult rodent spinal cord was described after injury and is thought to participate in recovery processes. Proliferation activity is scarce under physiological conditions, but still could be of importance, as in vitro studies showed that the spinal cord ependyma is an internal source of neural stem cells. Data from these studies indicate that there are regional differences in the distribution of proliferation activity along the rostro-caudal axis. We analyzed the proliferation activities in the ependyma within the entire extent of intact adult rat spinal cord. To identify proliferating cells we performed immunohistochemistry either for cell cycle S-phase marker BrdU or for the nuclear protein Ki-67. BrdU and Ki-67 positive cells were counted on sections selected from four spinal cord regions — cervical, thoracic, lumbar and sacral/coccygeal. Analysis showed that the number of BrdU positive cells within the ependyma was very low in all subdivisions of the spinal cord. Both BrdU and Ki-67 labeling revealed a significantly higher number of proliferating cells in the ependyma of sacrococcygeal part in comparison to all other spinal cord regions, suggesting that the caudal spinal cord might have potentially higher regeneration capacity compared to more rostral parts.

Neural Crest Stem Cells from Dental Tissues: A New Hope for Dental and Neural Regeneration

Several stem cell sources persist in the adult human body, which opens the doors to both allogeneic and autologous cell therapies. Tooth tissues have proven to be a surprisingly rich and accessible source of neural crest-derived ectomesenchymal stem cells (EMSCs), which may be employed to repair disease-affected oral tissues in advanced regenerative dentistry. Additionally, one area of medicine that demands intensive research on new sources of stem cells is nervous system regeneration, since this constitutes a therapeutic hope for patients affected by highly invalidating conditions such as spinal cord injury, stroke, or neurodegenerative diseases. However, endogenous adult sources of neural stem cells present major drawbacks, such as their scarcity and complicated obtention. In this context, EMSCs from dental tissues emerge as good alternative candidates, since they are preserved in adult human individuals, and retain both high proliferation ability and a neural-like phenotype in vitro. In this paper, we discuss some important aspects of tissue regeneration by cell therapy and point out some advantages that EMSCs provide for dental and neural regeneration. We will finally review some of the latest research featuring experimental approaches and benefits of dental stem cell therapy.

Differences between the neurogenic and proliferative abilities of Müller glia with stem cell characteristics and the ciliary epithelium from the adult human eye

Much controversy has arisen on the nature and sources of stem cells in the adult human retina. Whilst ciliary epithelium has been thought to constitute a source of neural stem cells, a population of Müller glia in the neural retina has also been shown to exhibit neurogenic characteristics. This study aimed to compare the neurogenic and proliferative abilities between these two major cell populations. It also examined whether differences exist between the pigmented and non-pigmented ciliary epithelium (CE) from the adult human eye. On this basis, Müller glia with stem cell characteristics and pigmented and non-pigmented CE were isolated from human neural retina and ciliary epithelium respectively. Expression of glial, epithelial and neural progenitor markers was examined in these cells following culture under adherent and non-adherent conditions and treatments to induce neural differentiation. Unlike pigmented CE which did not proliferate, non-pigmented CE cells exhibited limited proliferation in vitro, unless epidermal growth factor (EGF) was present in the culture medium to prolong their survival. In contrast, Müller glial stem cells (MSC) cultured as adherent monolayers reached confluence within a few weeks and continued to proliferative indefinitely in the absence of EGF. Both MSC and non-pigmented CE expressed markers of neural progenitors, including SOX2, PAX6, CHX10 and NOTCH. Nestin, a neural stem cell marker, was only expressed by MSC. Non-pigmented CE displayed epithelial morphology, limited photoreceptor gene expression and stained strongly for pigmented epithelial markers upon culture with neural differentiation factors. In contrast, MSC adopted neural morphology and expressed markers of retinal ganglion cells and photoreceptors when cultured under similar conditions.This study provides the first demonstration that pigmented CE possess different proliferative abilities from non-pigmented CE. It also showed that although non-pigmented CE express genes of retinal progenitors, they do not differentiate into neurons in vitro, as that seen with Müller glia that proliferate indefinitely in vitro and that acquire markers of retinal neurons in culture under neural differentiation protocols. From these observations it is possible to suggest that Müller glia that express markers of neural progenitors and become spontaneously immortalized in vitro constitute a potential source of retinal neurons for transplantation studies and fulfil the characteristics of true stem cells due to their proliferative and neurogenic ability.

Feline Bone Marrow-Derived Mesenchymal Stem Cells Express Several Pluripotent and Neural Markers and Easily Turn into Neural-Like Cells by Manipulation with Chromatin Modifying Agents and Neural Inducing Factors

Recent studies suggest that cellular therapies that utilize mesenchymal stem cells (MSCs), especially ones that have been neurally induced (NI), may provide a functional benefit in a wide range of neurological disorders. Recently, we developed a new method for the efficient generation of neural cells from human bone marrow (BM)-derived MSCs (hMSC). Neural induction was achieved by exposing cells simultaneously to chromatin-modifying agents and neural-inducing factors. When transplanted into injured spinal cords, these NI-hMSCs survived, differentiated, promoted tissue preservation, and significantly improved locomotor recovery of injured animals. In the current study, we sought to determine whether this methodological approach would be equally effective in generating neural-like cells from feline BM-derived MSCs (fMSC). Our long-term goal is to develop an autologous source of neural stem cells that can be used in cellular replacement therapies in large animal (feline) models of neurological disorders. Our results showed that fMSCs exhibited a neural morphology after 48-72 h of neural induction. Immunocytochemistry, ELISA, Western blot, and real-time RT-PCR studies revealed a higher level of expression of several pluripotent and neural genes in NI-fMSCs, the majority of which were expressed in untreated fMSCs at relatively low levels. We concluded that the expression of pluripotency- and neural-associated genes in unmodified fMSCs make them more pliable for reprogramming into a neural fate by manipulation with chromatin modifying agents and neural inducing factors.

Highlights in DD

“Highlights” calls attention to exciting advances in developmental biology that have recently been reported in Developmental Dynamics. Development is a broad field encompassing many important areas. To reflect this fact, the section spotlights significant discoveries that occur across the entire spectrum of developmental events and problems: from new experimental approaches, to novel interpretations of results, to noteworthy findings utilizing different developmental organisms. Not too late to remodel (Rapid Remodeling of Airway Vascular Architecture at Birth by Amy Ni, Erin Lashnits, Li-Chin Yao, Peter Baluk, and Donald M. McDonald, Dev Dyn 239:2354–2366) When form ceases to support function, it is time to remodel. Ni et al. discover that the mantra is not limited to kitchens and homes; tracheal vasculature also follows the same principle. Using the trachea as an easily studied representative of the airways, they document that embryonic day (E) 17.5 mice have a web-like primitive tracheal vascular plexus that is reminiscent of vascular architecture in the yolk sac. During postnatal stages P0–P3, an astounding 76% the vascular network is pruned, leaving a skeleton of vasculature that grows horizontally over the ladder-like cartilage rings lining the trachea. At P4, horizontal capillaries re-grow, and arterioles and venules begin to grow vertically between the rings, acquiring most features of adult vasculature by P7. Of interest, the vasculature of kidney, brain, and liver, all fail to undergo a similar overhaul at birth, suggesting that exposure to atmospheric oxygen may contribute to the remodeling phenomenon in the trachea. While the hypothesis remains to be tested, the authors do identify other mechanisms associated with vascular regression and re-growth. Hypoxic regions and hypoxia inducible factor (HIF1-α) correlate with vessel survival after birth, and survival of tracheal vasculature from P0 to P7 is dependent upon vascular endothelial growth factor (VEGF). Future work will focus on the roles of signaling pathways and changes in oxygen tension on vascular remodeling during postnatal development and disease. Smart screen (Essential Genes for Astroglial Development and Axon Pathfinding During Zebrafish Embryogenesis by Michael J.F. Barresi, Sean Burton, Kristina Dipietrantonio, Adam Amsterdam, Nancy Hopkins, and Rolf O. Karlstrom, Dev Dyn 239:2603–2618) Astroglia are the unsung heroes of neural development. Once believed to function solely as scaffold support for neurons, it is now understood that they play wide-ranging roles during neurogenesis such as in forming the blood–brain barrier, neural patterning, and regeneration. Despite their universal importance, little is known about astroglial development. To remedy this oversight, the authors screened an existing zebrafish mutant collection, for which the affected genes were already identified. They describe 25 mutants that are placed into one or more categories: axonal pathfinding, gliogenesis, glial patterning and neurogenesis. One important observation is that defects in glial patterning correlate with perturbed axon pathfinding, suggesting axon–glial interactions are important for axon scaffold formation. Another is the discovery of a new class of mutants affecting cell number of radial glial cells, the main source of neural stem cells in vertebrate embryos. The work also identifies potential novel roles for the affected genes, many of which are familiar signaling pathway components or transcription factors (i.e., chordin, tbx16). These intriguing preliminary findings double as jumping-off points from which to further the understanding of brain development. Green eggs and sperm (The ziwi Promoter Drives Germline-Specific Gene Expression in Zebrafish by David H. Leu and Bruce W. Draper, Dev Dyn 239:2714–2721) Here Leu and Draper unveil a tool that will be of interest to germ cell researchers and the zebrafish community at-large. They show that a 4.8-kb promoter of ziwi, which encodes an Argonaut class protein involved in Piwi-interacting RNA (piRNA) metabolism, can drive germline-specific, heterologous gene expression. Expression of the Tg(ziwi:EGFP) transgene initiates at 7 days postfertilization (dpf) in bipotential gonocytes and continues to be expressed after the onset of sexual differentiation (18–21 dpf) in all testis and ovary germ cells. Demonstrating the utility of the tool as a germ cell marker, Tg(ziwi:EGFP) aids the authors in defining new substages in stage-1A oocytes. What sets this germline-specific transgene apart from others, however, is that it is reliably expressed in premeiotic oocytes. The authors discuss the potential utility of the ziwi promoter in manipulating gene expression in the germline, producing genetic mosaic germlines, and speculate how the tool could propel the future of germ cell related technologies in zebrafish.

Evaluation of Bone Marrow- and Brain-Derived Neural Stem Cells in Therapy of Central Nervous System Autoimmunity

Adult subventricular zone (SVZ)-derived neural stem cells (NSCs) have therapeutic effects in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. However, SVZ precursor cells as a source of NSCs are not readily accessible for clinical application. In the present study, we demonstrate that NSCs derived from bone marrow (BM) cells exhibit comparable morphological properties as those derived from SVZ cells and possess a similar ability to differentiate into neurons, astrocytes, and oligodendrocytes both in vitro and in vivo. Importantly, both types of NSCs suppressed chronic experimental autoimmune encephalomyelitis to a comparable extent on transplantation. Mechanisms underlying the therapeutic effects of NSCs include immunomodulation in the periphery and the central nervous system (CNS), neuron/oligodendrocyte repopulation by transplanted cells, and enhanced endogenous remyelination and axonal recovery. Furthermore, we provide evidence for the trans-differentiation of transplanted BM-NSCs into neural cells in the CNS, while no fusion of these cells with host neural cells was detected. This is the first study that directly compares SVZ- versus BM-NSCs with regard to in vivo neural differentiation and anti-inflammatory and therapeutic effects on CNS inflammatory demyelination. Their virtually identical therapeutic potential, greater accessibility, and autologous properties make BM-NSCs a novel and highly applicable substitute for SVZ-NSCs in cell-based multiple sclerosis therapies.

Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal

Specialized cellular microenvironments, or “niches,” modulate stem cell properties, including cell number, self-renewal and fate decisions1,2. In the adult brain, niches that maintain a source of neural stem cells (NSCs) and neural progenitor cells (NPCs) are the subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus of the hippocampus3–5. The size of the NSC population of the SVZ at any time is the result of several ongoing processes, including self-renewal, cell differentiation, and cell death. Maintaining the balance between NSC and NPCs in the SVZ niche is critical to supply the brain with specific neural populations, both under normal conditions or after injury. A fundamental question relevant to both normal development and to cell-based repair strategies in the central nervous system is how the balance of different NSC and NPC populations is maintained in the niche. EGFR and Notch signaling pathways play fundamental roles during development of multicellular organisms6. In Drosophila and in C. elegans these pathways may have either cooperative or antagonistic functions7–9. In the SVZ, Notch regulates NSC identity and self-renewal, whereas EGFR specifically affects NPC proliferation and migration10–13. This suggests that interplay of these two pathways may maintain the balance between NSC and NPC numbers. Here we show that functional cell-cell interaction between NPCs and NSCs through epidermal growth factor receptor (EGFR) and Notch signaling plays a crucial role in maintaining the balance between these cell populations in the SVZ. Enhanced EGFR signaling in vivo results in the expansion of the NPC pool, and reduces NSC number and self-renewal. This occurs through a non-cell-autonomous mechanism involving EGFR-mediated regulation of Notch signaling. Our findings define a novel interaction between EGFR and Notch pathways in the adult SVZ, and thus provide a mechanism for NSC and NPC pool maintenance.

FGF but not EGF induces phosphorylation of the cAMP response element binding protein in olfactory mucosa-derived cell cultures

The stem/progenitor cells of the olfactory epithelium are potentially useful cells for autologous cell-based therapy because of their relative accessibility compared to other sources of neural stem cells. However, they have very limited potential to self-renew in vitro under growth factor stimulation compared to central nervous system-derived stem/progenitor cells. Using a sphere-forming assay and immunocytochemistry to identify cells that contained phosphorylated cAMP response element binding protein (pCREB) as an indicator of cell responsiveness to growth factor activation, we found that olfactory-spheres primed with FGF2 responded to FGF2 and EGF stimulation. In contrast, olfactory-spheres primed with EGF failed to respond to FGF2 or EGF stimulation despite the detection of FGFR1 and EGFR and their transcripts. These data demonstrate that FGF2 but not EGF permit the maintenance of a subset of cells responsive to FGF2 and EGF, whereas EGF induces unresponsive to either growth factor possibly via intrinsic mechanisms of regulation.

Angiogenic Factors Stimulate Growth of Adult Neural Stem Cells

BackgroundThe ability to grow a uniform cell type from the adult central nervous system (CNS) is valuable for developing cell therapies and new strategies for drug discovery. The adult mammalian brain is a source of neural stem cells (NSC) found in both neurogenic and non-neurogenic zones but difficulties in culturing these hinders their use as research tools [1], [2], [3], [4], [5], [6].Methodology/Principal FindingsHere we show that NSCs can be efficiently grown in adherent cell cultures when angiogenic signals are included in the medium. These signals include both anti-angiogenic factors (the soluble form of the Notch receptor ligand, Dll4) and pro-angiogenic factors (the Tie-2 receptor ligand, Angiopoietin 2). These treatments support the self renewal state of cultured NSCs and expression of the transcription factor Hes3, which also identifies the cancer stem cell population in human tumors. In an organotypic slice model, angiogenic factors maintain vascular structure and increase the density of dopamine neuron processes.Conclusions/SignificanceWe demonstrate new properties of adult NSCs and a method to generate efficient adult NSC cultures from various central nervous system areas. These findings will help establish cellular models relevant to cancer and regeneration.

Stem cells in the adult rat spinal cord: plasticity after injury and treadmill training exercise

Ependymal cells located around the central canal of the adult spinal cord are considered as a source of neural stem cells (NSCs) and represent an interesting pool of endogenous stem cells for repair strategies. Physical exercise is known to increase ependymal cell proliferation, while improving functional recovery. In this work, we further characterized those endogenous NSCs within the normal and injured adult rat spinal cord and investigated the effects of treadmill training using immunohistochemical and behavioral studies. In uninjured untrained rats, Sox-2, a NSC marker, was detected in all ependymal cells of the central canal, and also scattered throughout the parenchyma of the spinal cord. Within the lesion, Sox-2 expression increased transiently, while the number of nestin-positive ependymal cells increased with a concomitant enhancement of proliferation, as indicated by the mitotic markers Ki67 and bromo-deoxyuridine. Exercise, which improved functional recovery and autonomous micturition, maintained nestin expression in both injured and uninjured spinal cords, with a positive correlation between locomotor recovery and the number of nestin-positive cells.

Embryonic stem cell-derived neural stem cells improve spinal muscular atrophy phenotype in mice

Spinal muscular atrophy, characterized by selective loss of lower motor neurons, is an incurable genetic neurological disease leading to infant mortality. We previously showed that primary neural stem cells derived from spinal cord can ameliorate the spinal muscular atrophy phenotype in mice, but this primary source has limited translational value. Here, we illustrate that pluripotent stem cells from embryonic stem cells show the same potential therapeutic effects as those derived from spinal cord and offer great promise as an unlimited source of neural stem cells for transplantation. We found that embryonic stem cell-derived neural stem cells can differentiate into motor neurons in vitro and in vivo. In addition, following their intrathecal transplantation into spinal muscular atrophy mice, the neural stem cells, like those derived from spinal cord, survived and migrated to appropriate areas, ameliorated behavioural endpoints and lifespan, and exhibited neuroprotective capability. Neural stem cells obtained using a drug-selectable embryonic stem cell line yielded the greatest improvements. As with cells originating from primary tissue, the embryonic stem cell-derived neural stem cells integrated appropriately into the parenchyma, expressing neuron- and motor neuron-specific markers. Our results suggest translational potential for the use of pluripotent cells in neural stem cell-mediated therapies and highlight potential safety improvements and benefits of drug selection for neuroepithelial cells.

Plasticity and Neural Stem Cells in the Enteric Nervous System

The enteric nervous system (ENS) is a highly organized part of the autonomic nervous system, which innervates the whole gastrointestinal tract by several interconnected neuronal networks. The ENS changes during development and keeps throughout its lifespan a significant capacity to adapt to microenvironmental influences, be it in inflammatory bowel diseases or changing dietary habits. The presence of neural stem cells in the pre-, postnatal, and adult gut might be one of the prerequisites to adapt to changing conditions. During the last decade, the ENS has increasingly come into the focus of clinical neural stem cell research, forming a considerable pool of neural crest derived stem cells, which could be used for cell therapy of dysganglionosis, that is, diseases based on the deficient or insufficient colonization of the gut by neural crest derived stem cells; in addition, the ENS could be an easily accessible neural stem cell source for cell replacement therapies for neurodegenerative disorders or traumatic lesions of the central nervous system.

Generation of Functional Neural Artificial Tissue from Human Umbilical Cord Blood Stem Cells

Stem cell-based regenerative neurology is an emerging concept for treatment of diseases of central nervous system. Among variety of proposed procedures, one of the most promising is refilling of cystic cavities of injured brain parenchyma with artificial neural tissue. Recent studies revealed that after allogenic transplantation in rodents these tissue-engineered entities were shown efficient in repair of hypoxic/ischemic brain injury. Human umbilical cord blood (HUCB) was recognized to be an efficient and noncontroversial source of neural stem cells (NSC). The main purpose of this study was to generate HUCB-derived neural artificial tissue and investigate their functional properties. Neural organoids formed on human-originated biodegradable scaffolds within 3 weeks and resembled niche structure where immature stem cells (Oct4+ and Sox2+) and proliferating neuroblasts (Nestin+, GFAP+, and Ki67+) were present. Such aggregates were placed on multi-electrode chips and differentiated toward mature neurons (TUJ1+ and MAP2+). These three-dimensional aggregates in contrast to two-dimensional cultures formed functional circuits and generated spontaneous field/action potentials. Our results indicate that three-dimensional environment facilitates maturation of HUCB-derived NSC what should be considered regarding regenerative medicine application.

New Source of Neural Stem Cells at the Tail End of the Spinal Cord

New Source of Neural Stem Cells at the Tail End of the Spinal Cord

The Center of the Spinal Cord May Be Central to Its Repair

A recent PLoS Biology report from Meletis et al. (2008) strongly suggests that ependymal cells are a key source of endogenous stem cells in the spinal cord. Advances in understanding endogenous neural stem cells may facilitate repair of the injured central nervous system.