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Biomedical subjects

Philippe Taupin

Publications and source records attributed to Philippe Taupin.

At least 19 recordsLinked to original sources
PubMed2006

BrdU immunohistochemistry for studying adult neurogenesis: paradigms, pitfalls, limitations, and validation.

Bromodeoxyuridine (BrdU) is a thymidine analog that incorporates DNA of dividing cells during the S-phase of the cell cycle. As such, BrdU is used for birth dating and monitoring cell proliferation. BrdU immunohistochemistry has been instrumental for the study of the development of the nervous system, and to confirm that neurogenesis occurs in the adult mammalian brain, including in human. However, the use of BrdU for studying neurogenesis is not without pitfalls and limitations. BrdU is a toxic and mutagenic substance. It triggers cell death, the formation of teratomas, alters DNA stability, lengthens the cell cycle, and has mitogenic, transcriptional and translational effects on cells that incorporate it. All of which have profound consequences on neurogenesis. BrdU is not a marker of the S-phase of the cell cycle. As a thymidine analog, it is a marker of DNA synthesis. Therefore, studying neurogenesis with BrdU requires distinguishing cell proliferation and neurogenesis from other events involving DNA synthesis, like DNA repair, abortive cell cycle reentry and gene duplication. BrdU labeling is currently the most used technique for studying adult neurogenesis in situ. However in many instances, appropriate controls have been overlooked and events reported as the generation of new neuronal cells in the adult brain misinterpreted, which makes BrdU labeling one of the most misused techniques in neuroscience.

Animals↗
PubMed2006

Neurogenesis in the adult central nervous system.

Contrary to the long-held dogma, neurogenesis occurs throughout adulthood, and neural stem cells reside in the adult central nervous system (CNS) in mammals. The developmental process of the brain may thus never end, and the brain may be amenable to repair. Neurogenesis is modulated in a wide variety of physiological and pathological conditions, and is involved in processes such as learning and memory and depression. However, the relative contribution of newly generated neuronal cells to these processes, as well as to CNS plasticity, remains to be determined. Thus, not only neurogenesis contributes to reshaping the adult brain, it will ultimately lead us to redefine our knowledge and understanding of the nervous system.

Animals↗
PubMed2006

Derivation of embryonic stem cells for cellular therapy: challenges and new strategies.

Cellular therapy is the replacement of unhealthy or damaged cells or tissues by new ones. Embryonic stem (ES) cells are undifferentiated cells that can generate all the cell types of the body, and therefore hold the potential to cure a broad range of diseases and injuries, ranging from diabetes, liver and heart diseases, to neurological diseases, such as Alzheimer's and Parkinson's diseases. The derivation of human ES (hES) cells has been a major step toward bringing ES cell research to therapy. However, there are several challenges to the advent of ES cell research to therapy. Among them, the derivation of hES cell lines devoid of animal contaminants, the maintenance of their normal karyotypes, their potentials to form tumors upon grafting, and the derivation of isogenic hES cell lines. Stringent ethical and political guidelines are also limiting the use of human embryos for research, thereby limiting progress in ES cell research. Recently, several investigators have devised protocols to derive hES cells free of feeder layer and animal serum, reported that some established cell lines remain stable overtime, pre-differentiated ES cells in vitro to circumvent the risk of tumor formation, and derived ES cell lines without destroying embryos. In this manuscript, we will review and discuss these developments that may unlock ES cell research and therapy.

Animals↗
PubMed2006

Stroke-induced neurogenesis: physiopathology and mechanisms.

Long-term disabilities are the main outcome of cerebral strokes, though some of the deficits show receding signs in the weeks and months following the "brain attack". Studies show that neurogenesis is induced in the hippocampus and subventricular zone (SVZ) in animal models of ischemia, and that new neurons are generated at the sites of degeneration, where they replace some of the lost nerve cells. The enhanced neurogenesis suggests the involvement of the hippocampus and SVZ in the physiopathology of cerebral strokes, and the generation of new neuronal cells at the sites of degeneration suggests that the central nervous system (CNS) may attempt to repair itself. In this manuscript, we will review the studies on adult neurogenesis in cerebral strokes, discuss the contribution of adult neurogenesis to the physiopathology of strokes, and its underlying mechanisms.

Animals↗
PubMed2006

Adult neurogenesis and neuroplasticity.

After cerebral strokes and traumatic brain injuries (TBIs), there is a striking amount of neurological recovery in the following months and years, despite often-permanent structural damage. Though the mechanisms underlying such recovery are not fully understood, properties of plasticity of the central nervous system (CNS), such as the reorganization of the pre-existing network and axonal sprouting have been implicated in the recovery. With the recent evidences that neurogenesis occurs in the adult brain, and neural stem cells (NSCs) reside in the adult CNS, the involvement of newly generated neuronal cells in the recovery following injury to the CNS remains to be established. Neurogenesis is increased bilaterally in the dentate gyrus (DG) and the subventicular zone (SVZ) after cerebral strokes and TBIs, and new neuronal cells are generated at the sites of injury, where they replace some of the degenerated nerve cells. Newly generated neuronal cells at the sites of injury may represent an attempt by the CNS to regenerate itself after injury, whereas the increased neurogenesis in the DG and SVZ would also contribute to the CNS plasticity. Thus, injury-induced neurogenesis may contribute to the recovery and plasticity of the CNS.

Animals↗
PubMed2006

HuCNS-SC (StemCells).

HuCNS-SC, a proprietary human neural stem cells product, is being developed as a cellular therapy for the potential treatment of Batten disease, one of a group of disorders known as neural ceroid lipofuscinoses (NCL). Developer StemCells is also investigating the therapy for spinal cord injury and other central nervous system disorders, such as demyelinating disease, stroke and Alzheimer's disease. A phase I trial of HuCNS-SC for infantile and late-infantile NCL has been initiated, following the March 2006 U.S. Food and Drug Administration approval of StemCells' investigational new drug application.

Central Nervous System↗
PubMed2006

OTI-010 Osiris Therapeutics/JCR Pharmaceuticals.

Osiris Therapeutics is developing the donor-derived mesenchymal stem cell (MSC) therapy OTI-010, which repopulates the bone marrow stroma and thus supports engraftment of hematopoietic stem cells from the same donor. This stem cell therapy, which has been awarded Orphan Drug status, is currently in development for the potential enhancement of bone marrow transplants in cancer patients, for the prevention of graft versus host disease (GVHD), and for the treatment of Crohn's disease. Japanese licensee JCR Pharmaceuticals is investigating the therapy for the potential treatment of GVHD in patients undergoing bone marrow transplantation to treat leukemia. Phase II clinical trials in acute gastrointestinal GVHD and in adult and pediatric patients with treatment-refractory severe GVHD are currently underway.

Adolescent↗
PubMed2006

The therapeutic potential of adult neural stem cells.

Neural stem cells (NSCs) are self-renewing, multipotent cells that generate the neuronal and glial cells of the nervous system. In mammals, contrary to long-held belief, neurogenesis occurs in the adult brain, and NSCs reside in the adult central nervous system. Thus, the brain may be amenable to repair following damage, and new avenues for cell-based therapy are being considered for the treatment of brain disease and injury, such as the stimulation of endogenous progenitor cells, the transplantation of adult-derived neural progenitor and stem cells, and, in particular, autologous cell transplantation. Although significant advances in this field have been made over the past decade, the adult NSC remains an elusive cell for study, and researchers are facing multiple challenges to the development of therapeutic applications from adult NSC research. Among these challenges are the identification and characterization of NSCs in vivo and in vitro, the understanding of the physiology of newly generated neuronal cells in the adult brain, the stimulation of endogenous progenitor cells to promote functional recovery, and the isolation and culture of homogenous populations of neural progenitor or stem cells from the adult brain for cell-based therapy.

Adult Stem Cells↗
PubMed2006

Adult neurogenesis in mammals.

With the recent confirmation that neurogenesis occurs in the adult brain, and that neural stem cells reside in the adult central nervous system (CNS), the function of newly generated neuronal cells in the adult brain is the source of intense research and debate. Neurogenesis is modulated by a wide variety of physiopathological conditions and environmental stimuli, offering the possibility that newly generated neuronal cells might be functionally associated with the response to these processes. Newly generated neuronal cells in the hippocampus have also been implicated in mechanisms of learning, memory and depression. However, a number of studies have challenged some of these findings, and the roles of newly generated neuronal cells in the functioning of the CNS remain to be fully understood. Neurogenesis has been shown to increase bilaterally in the adult brain and new neuronal cells are generated at sites of degeneration in the brain during disease and after injuries. Taken together, these findings suggest that new neuronal cells may be involved in processes such as homeostasis of brain tissue, regeneration, plasticity, and neuroadaptation.

Animals↗
PubMed2006

Neural progenitor and stem cells in the adult central nervous system.

Neurogenesis occurs in the adult brain, and neural stem cells (NSCs) reside in the adult central nervous system (CNS). In the adult brain, newly generated neuronal cells would originate from a population of glial cells with stem cells properties, and be involved in processes such as learning and memory, depression, and in regenerative attempts in the diseased brain and after injuries. In human, a recent study reported no evidence of migrating neural progenitor cells along the subventricular zone (SVZ) to the olfactory bulb (OB), contrary to other species, highlighting the particularity of adult neurogenesis in human. Though the origin and contribution of newly generated neuronal cells to CNS pathophysiology remain to be fully understood, the discovery that NSCs reside in the adult CNS force us to re-evaluate our knowledge and understanding of brain functioning, and suggest that the adult CNS may be amenable to repair. In this manuscript,we will review the recent data, debates and controversies on the identification, origin and function of newly generated neuronal cells in the adult brain, in human and in other species. We will discuss their contribution and significance to CNS pathophysiology, and for cellular therapy.

Adult Stem Cells↗
PubMed2005

Adult neurogenesis in the mammalian central nervous system: functionality and potential clinical interest.

In the past decades, much evidence has confirmed that neurogenesis occurs in the adult brain and that neural stem cells reside in the adult central nervous system, overturning the long-held dogma that we are born with a certain number of nerve cells and that the brain cannot generate new neurons and renew itself. In the adult brain, neurogenesis occurs mainly in two areas: the hippocampus and the subventricular zone, and self-renewing, multipotent neural stem cells have been isolated and characterized in vitro from various regions of the adult central nervous system. Though significant advances have been made in this field of research, the identification and function of neural stem cells in the adult central nervous system remain the source of debate and controversy. Neurogenesis is modulated by several normal and pathologic conditions, suggesting the involvement of the hippocampus and the subventricular zone in a broad range of functions, and that environmental stimuli and pathological conditions may have long-term consequences on the architecture and functioning of the central nervous system. Neurogenesis is involved in processes such as learning, memory, and depression, and may also be involved in regenerative attempts after injuries to the central nervous system. However, the contribution of neurogenesis to these phenomena remains to be elucidated. Neural stem cells also hold the promise to cure a broad range of neurological diseases and injuries. Cell therapeutic interventions may involve both cell transplantation and the stimulation of endogenous neural progenitor cells.

Animals↗
PubMed2004

Microfabricated platform for studying stem cell fates.

Platforms that allow parallel, quantitative analysis of single cells will be integral to realizing the potential of postgenomic biology. In stem cell biology, the study of clonal stem cells in multiwell formats is currently both inefficient and time-consuming. Thus, to investigate low-frequency events of interest, large sample sizes must be interrogated. We report a simple, versatile, and efficient micropatterned arraying system conducive to the culture and dynamic monitoring of stem cell proliferation. This platform enables: 1) parallel, automated, long-term ( approximately days to weeks), live-cell microscopy of single cells in culture; 2) tracking of individual cell fates over time (proliferation, apoptosis); and 3) correlation of differentiated progeny with founder clones. To achieve these goals, we used microfabrication techniques to create an array of approximately 10,000 microwells on a glass coverslip. The dimensions of the wells are tunable, ranging from 20 to >500 microm in diameter and 10-500 microm in height. The microarray can be coated with adhesive proteins and is integrated into a culture chamber that permits rapid (approximately min), addressable monitoring of each well using a standard programmable microscope stage. All cells share the same media (including paracrine survival signals), as opposed to cells in multiwell formats. The incorporation of a coverslip as a substrate also renders the platform compatible with conventional, high-magnification light and fluorescent microscopy. We validated this approach by analyzing the proliferation dynamics of a heterogeneous adult rat neural stem cell population. Using this platform, one can further interrogate the response of distinct stem cell subpopulations to microenvironmental cues (mitogens, cell-cell interactions, and cell-extracellular matrix interactions) that govern their behavior. In the future, the platform may also be adapted for the study of other cell types by tailoring the surface coatings, microwell dimensions, and culture environment, thereby enabling parallel investigation of many distinct cellular responses.

Cell Count↗
PubMed2004

Expression and function of orphan nuclear receptor TLX in adult neural stem cells.

The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains and is highly expressed in the adult brain. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behaviour. Here we show that TLX maintains adult neural stem cells in an undifferentiated, proliferative state. We show that TLX-expressing cells isolated by fluorescence-activated cell sorting (FACS) from adult brains can proliferate, self-renew and differentiate into all neural cell types in vitro. By contrast, TLX-null cells isolated from adult mutant brains fail to proliferate. Reintroducing TLX into FACS-sorted TLX-null cells rescues their ability to proliferate and to self-renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells.

Aging↗