Author
Maurice Vroemen
Other affiliations: Ludwig Maximilian University of Munich, Technische Universität München
Bio: Maurice Vroemen is an academic researcher from University of Regensburg. The author has contributed to research in topics: Neural stem cell & Spinal cord injury. The author has an hindex of 14, co-authored 17 publications receiving 2172 citations. Previous affiliations of Maurice Vroemen include Ludwig Maximilian University of Munich & Technische Universität München.
Papers
More filters
TL;DR: It is demonstrated that quantification of DCX‐expressing cells allows for an accurate measurement of modulations in the rate of adult neurogenesis, and DCX is a valuable alternative to techniques currently used to measure the levels of Neurogenesis.
Abstract: Progress in the field of neurogenesis is currently limited by the lack of tools enabling fast and quantitative analysis of neurogenesis in the adult brain Doublecortin (DCX) has recently been used as a marker for neurogenesis However, it was not clear whether DCX could be used to assess modulations occurring in the rate of neurogenesis in the adult mammalian central nervous system following lesioning or stimulatory factors Using two paradigms increasing neurogenesis levels (physical activity and epileptic seizures), we demonstrate that quantification of DCX-expressing cells allows for an accurate measurement of modulations in the rate of adult neurogenesis Importantly, we excluded induction of DCX expression during physiological or reactive gliogenesis and excluded also DCX re-expression during regenerative axonal growth Our data validate DCX as a reliable and specific marker that reflects levels of adult neurogenesis and its modulation We demonstrate that DCX is a valuable alternative to techniques currently used to measure the levels of neurogenesis Importantly, in contrast to conventional techniques, analysis of neurogenesis through the detection of DCX does not require in vivo labelling of proliferating cells, thereby opening new avenues for the study of human neurogenesis under normal and pathological conditions
904 citations
TL;DR: Alginate-based ACH represent a promising strategy to induce directed nerve regrowth following spinal cord injury and adult neural progenitor cells (NPC), which have been shown to promote cell-contact-mediated axon regeneration, can be seeded into alginates as a prerequisite to further improve the regenerative capacity of these artificial growth supportive matrices.
346 citations
TL;DR: Efficient growth of adult NSCs in Neurobasal medium containing B27 supplement under clonal and low-density conditions in the absence of serum or conditioned medium is described, providing an important step toward the development of standardized protocols for highly efficient in vitro expansion of N SCs from the adult central nervous system.
237 citations
TL;DR: It is demonstrated that adult neural progenitor cells will survive after transplantation into the acutely injured spinal cord and the observed oligodendroglial and astroglials differentiation and integration along axonal pathways represent important prerequisites for potential remyelination and support of axonal regrowth.
Abstract: The main rationale for cell-based therapies following spinal cord injury are: (i) replacement of degenerated spinal cord parenchyma by an axon growth supporting scaffold; (ii) remyelination of regenerating axons; and (iii), local delivery of growth promoting molecules. A potential source to meet these requirements is adult neural progenitor cells, which were examined in the present study. Fibroblast growth factor 2-responsive adult spinal cord-derived syngenic neural progenitor cells were either genetically modified in vitro to express green fluorescent protein (GFP) using retroviral vectors or prelabelled with bromodeoxyuridine (BrdU). Neural progenitor cells revealed antigenic properties of neurons and glial cells in vitro confirming their multipotency. This differentiation pattern was unaffected by retroviral transduction. GFP-expressing or BrdU-prelabelled neural progenitor cells were grafted as neurospheres directly into the acutely injured rat cervical spinal cord. Animals with lesions only served as controls. Three weeks postoperatively, grafted neural progenitor cells integrated along axonal profiles surrounding the lesion site. In contrast to observations in culture, grafted neural progenitor cells differentiated only into astro- and oligodendroglial lineages, supporting the notion that the adult spinal cord provides molecular cues for glial, but not for neuronal, differentiation. This study demonstrates that adult neural progenitor cells will survive after transplantation into the acutely injured spinal cord. The observed oligodendroglial and astroglial differentiation and integration along axonal pathways represent important prerequisites for potential remyelination and support of axonal regrowth.
206 citations
TL;DR: It is demonstrated that the transcription factor E2F1, which is targeted by several signaling cascades that are activated by growth factors, is involved in neurogenesis in the adult brain.
115 citations
Cited by
More filters
TL;DR: This review will provide a comprehensive overview of general properties of alginate and its hydrogels, their biomedical applications, and suggest new perspectives for future studies with these polymers.
5,372 citations
TL;DR: It is reported that, unlike other brain cancers, the lethal glioblastoma multiforme contains neural precursors endowed with all of the critical features expected from neural stem cells.
Abstract: Transformed stem cells have been isolated from some human cancers. We report that, unlike other brain cancers, the lethal glioblastoma multiforme contains neural precursors endowed with all of the critical features expected from neural stem cells. Similar, yet not identical, to their normal neural stem cell counterpart, these precursors emerge as unipotent (astroglial) in vivo and multipotent (neuronal-astroglial-oligodendroglial) in culture. More importantly, these cells can act as tumor-founding cells down to the clonal level and can establish tumors that closely resemble the main histologic, cytologic, and architectural features of the human disease, even when challenged through serial transplantation. Thus, cells possessing all of the characteristics expected from tumor neural stem cells seem to be involved in the growth and recurrence of adult human glioblastomas multiforme.
2,489 citations
TL;DR: It is shown that adult hippocampal stem/progenitor cells (AHPs) express receptors and signalling components for Wnt proteins, which are key regulators of neural stem cell behaviour in embryonic development, and that the Wnt/β-catenin pathway is active and that Wnt3 is expressed in the hippocampal neurogenic niche.
Abstract: Neural stem/progenitor cells in the adult brain are able to generate both the brain's major cell types: glial cells, which are non-neuronal, and the active nerve cells or neurons. Neurons are produced in just two regions of the brain. Lie et al. have now identified a protein family that instructs the adult neural stem cells to produce neurons, rather than glial cells. The signal molecule Wnt3 is shown to be crucial for the production of neurons in the adult hippocampus, a region believed to be involved in learning and memory formation. Ultimately these studies may help develop therapies to repair brain damage caused by disease or trauma. The generation of new neurons from neural stem cells is restricted to two regions of the adult mammalian central nervous system: the subventricular zone of the lateral ventricle, and the subgranular zone of the hippocampal dentate gyrus1. In both regions, signals provided by the microenvironment regulate the maintenance, proliferation and neuronal fate commitment of the local stem cell population1. The identity of these signals is largely unknown. Here we show that adult hippocampal stem/progenitor cells (AHPs) express receptors and signalling components for Wnt proteins, which are key regulators of neural stem cell behaviour in embryonic development2. We also show that the Wnt/β-catenin pathway is active and that Wnt3 is expressed in the hippocampal neurogenic niche. Overexpression of Wnt3 is sufficient to increase neurogenesis from AHPs in vitro and in vivo. By contrast, blockade of Wnt signalling reduces neurogenesis from AHPs in vitro and abolishes neurogenesis almost completely in vivo. Our data show that Wnt signalling is a principal regulator of adult hippocampal neurogenesis and provide evidence that Wnt proteins have a role in adult hippocampal function.
1,445 citations
TL;DR: This work has shown that in two areas of the adult brain, new neurons are generated throughout life and form an integral part of the normal functional circuitry, revealing a plastic mechanism by which the brain's performance can be optimized for a given environment.
Abstract: The adult brain is a plastic place. To ensure that the mature nervous system's control of behaviour is flexible in the face of a varying environment, morphological and physiological changes are possible at many levels, including that of the entire cell. In two areas of the adult brain - the olfactory bulb and the dentate gyrus - new neurons are generated throughout life and form an integral part of the normal functional circuitry. This process is not fixed, but highly modulated, revealing a plastic mechanism by which the brain's performance can be optimized for a given environment. The functional benefits of this whole-cell plasticity, however, remain a matter for debate.
1,384 citations
TL;DR: Together, the data provide first evidence that CD133(+) CSC maintain only a subset of primary glioblastomas, with apparent stem cell-like properties but distinct molecular profiles and growth characteristics in vitro and in vivo.
Abstract: Although glioblastomas show the same histologic phenotype, biological hallmarks such as growth and differentiation properties vary considerably between individual cases. To investigate whether different subtypes of glioblastomas might originate from different cells of origin, we cultured tumor cells from 22 glioblastomas under medium conditions favoring the growth of neural and cancer stem cells (CSC). Secondary glioblastoma (n = 7)-derived cells did not show any growth in the medium used, suggesting the absence of neural stem cell-like tumor cells. In contrast, 11/15 primary glioblastomas contained a significant CD133(+) subpopulation that displayed neurosphere-like, nonadherent growth and asymmetrical cell divisions yielding cells expressing markers characteristic for all three neural lineages. Four of 15 cell lines derived from primary glioblastomas grew adherently in vitro and were driven by CD133(-) tumor cells that fulfilled stem cell criteria. Both subtypes were similarly tumorigenic in nude mice in vivo. Clinically, CD133(-) glioblastomas were characterized by a lower proliferation index, whereas glial fibrillary acidic protein staining was similar. GeneArray analysis revealed 117 genes to be differentially expressed by these two subtypes. Together, our data provide first evidence that CD133(+) CSC maintain only a subset of primary glioblastomas. The remainder stems from previously unknown CD133(-) tumor cells with apparent stem cell-like properties but distinct molecular profiles and growth characteristics in vitro and in vivo.
1,127 citations