Can bone marrow-derived multipotent adult progenitor cells regenerate infarcted myocardium?

Objectives: To assess the functional effects of multipotent adult progenitor cells (MAPCs) transplanted in a rat model of chronic myocardial infarction.

Methods: Forty-four rats underwent coronary ligation and, 14 days later, were randomly allocated to receive in-scar injections (5 x 10(6) cells/150 microL) of green fluorescent protein (eGFP)-transduced allogeneic MAPCs (n = 25) or culture medium (controls, n = 19). Nine of the MAPC-treated hearts were employed for functional studies while the remaining 16 received cells co-labeled with Resovist and were only used for serial histological assessments.

Chronic cocaine exposure impairs progenitor proliferation but spares survival and maturation of neural precursors in adult rat dentate gyrus.

Recent observations indicate that drugs of abuse, including alcohol and opiates, impair adult neurogenesis in the hippocampus. We have studied in rats the impact of cocaine treatment (20 mg/kg, daily, i.p.

Origin of oligodendrocytes in the subventricular zone of the adult brain.

Glial fibrillary acidic protein (GFAP)-positive astrocytes (type B cells) in the subventricular zone (SVZ) generate large numbers of new neurons in the adult brain. SVZ stem cells can also generate oligodendrocytes in vitro, but it is not known whether these adult primary progenitors generate oligodendrocytes in vivo. Myelin repair and oligodendrocyte formation in the adult brain is instead associated with glial-restricted progenitors cells, known as oligodendrocyte progenitor cells (OPCs).

PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling.

Neurons and oligodendrocytes are produced in the adult brain subventricular zone (SVZ) from neural stem cells (B cells), which express GFAP and have morphological properties of astrocytes. We report here on the identification B cells expressing the PDGFRalpha in the adult SVZ. Specifically labeled PDGFRalpha expressing B cells in vivo generate neurons and oligodendrocytes.

Survival and differentiation of embryonic neural explants on different biomaterials.

Biomaterials prepared from polyacrylamide, ethyl acrylate (EA), and hydroxyethyl acrylate (HEA) in various blend ratios, methyl acrylate and chitosan, were tested in vitro as culture substrates and compared for their ability to be colonized by the cells migrating from embryonic brain explants. Neural explants were isolated from proliferative areas of the medial ganglionic eminence and the cortical ventricular zone of embryonic rat brains and cultured in vitro on the different biomaterials. Chitosan, poly(methyl acrylate), and the 50% wt copolymer of EA and HEA were the most suitable substrates to promote cell attachment and differentiation of the neural cells among those tested.

Lentiviral vectors mediate efficient and stable gene transfer in adult neural stem cells in vivo.

Modulation of adult neurogenesis may offer new therapeutic strategies for various brain disorders. In the adult mammalian brain the subventricular zone (SVZ) of the lateral ventricle is a region of continuous neurogenesis. Lentiviral vectors stably integrate into dividing and nondividing cells, in contrast to retroviral vectors, which integrate only into dividing cells.

Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum.

Recent studies have revealed that the adult mammalian brain has the capacity to regenerate some neurons after various insults. However, the precise mechanism of insult-induced neurogenesis has not been demonstrated. In the normal brain, GFAP-expressing cells in the subventricular zone (SVZ) of the lateral ventricles include a neurogenic cell population that gives rise to olfactory bulb neurons only.

Composition and organization of the SCZ: a large germinal layer containing neural stem cells in the adult mammalian brain.

Two known germinal zones continue to generate new neurons and glia in the adult mammalian brain: the subventricular zone (SVZ), lining the lateral walls of the lateral ventricle, and the subgranular zone of the dentate gyrus. Here we describe a region we will refer to as the subcallosal zone (SCZ). The SCZ is a caudal extension of the SVZ that is no longer associated to an open ventricle.

Environmental enrichment promotes neurogenesis and changes the extracellular concentrations of glutamate and GABA in the hippocampus of aged rats.

The aim of the present study was to investigate the effects of environmental enrichment on the neurogenesis and the extracellular concentrations of glutamate and GABA in the hippocampus of freely moving young and aged rats. Male Wistar rats of 2 (young) and 25 (old) months of age were housed during 8 weeks in an enriched environment; control rats were kept in individual plastic cages during that same period of time. Rats were injected intraperitoneally with bromodeoxyuridine (BrdU; 40 mg/kg; 7 days) during the fourth week of the housing period to detect neurogenesis in the dentate gyrus (DG) of the hippocampus.

Absence of dysferlin alters myogenin expression and delays human muscle differentiation "in vitro".

Mutations in dysferlin cause a type of muscular dystrophy known as dysferlinopathy. Dysferlin may be involved in muscle repair and differentiation. We compared normal human skeletal muscle cultures expressing dysferlin with muscle cultures from dysferlinopathy patients.

Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior.

Hormonal imbalances are involved in many of the age-related pathologies, as neurodegenerative and psychiatric diseases. Specifically, thyroid state alterations in the adult are related to psychological changes and mood disorders as depression. The dentate gyrus of the hippocampal formation undergoes neurogenesis in adult mammals including humans.

Loss of p53 induces changes in the behavior of subventricular zone cells: implication for the genesis of glial tumors.

The role of multipotential progenitors and neural stem cells in the adult subventricular zone (SVZ) as cell-of-origin of glioblastoma has been suggested by studies on human tumors and transgenic mice. However, it is still unknown whether glial tumors are generated by all of the heterogeneous SVZ cell types or only by specific subpopulations of cells. It has been proposed that transformation could result from lack of apoptosis and increased self-renewal, but the definition of the properties leading to neoplastic transformation of SVZ cells are still elusive.

New neurons follow the flow of cerebrospinal fluid in the adult brain.

In the adult brain, neuroblasts born in the subventricular zone migrate from the walls of the lateral ventricles to the olfactory bulb. How do these cells orient over such a long distance and through complex territories? Here we show that neuroblast migration parallels cerebrospinal fluid (CSF) flow. Beating of ependymal cilia is required for normal CSF flow, concentration gradient formation of CSF guidance molecules, and directional migration of neuroblasts.

Thymidine analogs are transferred from prelabeled donor to host cells in the central nervous system after transplantation: a word of caution.

Thymidine analogs, including bromodeoxyuridine, chlorodeoxyuridine, iododeoxyuridine, and tritiated thymidine, label dividing cells by incorporating into DNA during S phase of cell division and are widely employed to identify cells transplanted into the central nervous system. However, the potential for transfer of thymidine analogs from grafted cells to dividing host cells has not been thoroughly tested. We here demonstrate that graft-derived thymidine analogs can become incorporated into host neural precursors and glia.

Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells.

The lateral wall of the lateral ventricle in the human brain contains neural stem cells throughout adult life. We conducted a cytoarchitectural and ultrastructural study in complete postmortem brains (n = 7) and in postmortem (n = 42) and intraoperative tissue (n = 43) samples of the lateral walls of the human lateral ventricles. With varying thickness and cell densities, four layers were observed throughout the lateral ventricular wall: a monolayer of ependymal cells (Layer I), a hypocellular gap (Layer II), a ribbon of cells (Layer III) composed of astrocytes, and a transitional zone (Layer IV) into the brain parenchyma.

Functional neural stem cells derived from adult bone marrow.

Pluripotent hematopoietic cells from adult bone marrow may give rise not only to neurons, oligodendrocytes and astrocytes after transplantation into newborn brains, but also to neural stem cells (NSC). These NSC localize to both the ventricular epithelium and subventricular zone, persist in the transplanted brain, and may generate neurospheres 1 month after transplant, which after in vitro expansion differentiate into the different neural lineages. Furthermore, the bone marrow-derived NSC differentiate in vivo into functional oligodendrocytes and neurons following demyelinating lesions, thus, demonstrating the ability of adult bone marrow progenitors to generate self-renewing, functional neural stem cells, validating this approach as an alternative source of long-lasting neural stem cells with therapeutic implications in neurodegenerative diseases.

Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis.

Ependymal cells on the walls of brain ventricles play essential roles in the transport of CSF and in brain homeostasis. It has been suggested that ependymal cells also function as stem cells. However, the proliferative capacity of mature ependymal cells remains controversial, and the developmental origin of these cells is not known.

Radial glia give rise to adult neural stem cells in the subventricular zone.

Neural stem cells with the characteristics of astrocytes persist in the subventricular zone (SVZ) of the juvenile and adult brain. These cells generate large numbers of new neurons that migrate through the rostral migratory stream to the olfactory bulb. The developmental origin of adult neural stem cells is not known.

Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus.

New neurons continue to be born in the subgranular zone (SGZ) of the dentate gyrus in the hippocampus of adult mammals, including humans. Previous work has shown that astrocytes function as the progenitors of these new neurons through immature intermediate D cells. In the first part of the present study, we determined the structure of each of these progenitors and how they are organized in three dimensions.

Coexistence of Wolbachia with Buchnera aphidicola and a secondary symbiont in the aphid Cinara cedri.

Intracellular symbiosis is very common in the insect world. For the aphid Cinara cedri, we have identified by electron microscopy three symbiotic bacteria that can be characterized by their different sizes, morphologies, and electrodensities. PCR amplification and sequencing of the 16S ribosomal DNA (rDNA) genes showed that, in addition to harboring Buchnera aphidicola, the primary endosymbiont of aphids, C.

Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells.

Cardiomyocyte regeneration is limited in adult life. Thus, the identification of a putative source of cardiomyocyte progenitors is of great interest to provide a usable model in vitro and new perspective in regenerative therapy. As adipose tissues were recently demonstrated to contain pluripotent stem cells, the emergence of cardiomyocyte phenotype from adipose-derived cells was investigated.

Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes.

Recent studies have suggested that bone marrow cells possess a broad differentiation potential, being able to form new liver cells, cardiomyocytes and neurons. Several groups have attributed this apparent plasticity to 'transdifferentiation'. Others, however, have suggested that cell fusion could explain these results.

Selective impairment of hippocampal neurogenesis by chronic alcoholism: protective effects of an antioxidant.

A major pathogenic mechanism of chronic alcoholism involves oxidative burden to liver and other cell types. We show that adult neurogenesis within the dentate gyrus of the hippocampus is selectively impaired in a rat model of alcoholism, and that it can be completely prevented by the antioxidant ebselen. Rats fed for 6 weeks with a liquid diet containing moderate doses of ethanol had a 66.

Postnatal development of radial glia and the ventricular zone (VZ): a continuum of the neural stem cell compartment.

The germinal neuroepithelium, or ventricular zone (VZ) of the developing fetal brain, was once thought to transform into the non-germinal ependymal zone of the postnatal and adult brain. Persistence of neural stem cells and neurogenesis throughout postnatal life, however, suggests a continuum between embryonic and adult germinal brain centers. Here, we suggest that developmental changes in anatomy and molecular marker expression in the ventricular walls (the principal germinal centers of the brain) may have misled us into current interpretations of VZ transformation from a germinal to a non-germinal epithelium.

Nuclear translocation of nuclear transcription factor-kappa B by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons.

We describe a new molecular mechanism of cell death by excitotoxicity mediated through nuclear transcription factor kappa B (NF kappa B) in rat embryonic cultures of dopaminergic neurons. Treatment of mesencephalic cultures with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) resulted in a number of changes that occurred selectively in dopaminergic neurons, including persistent elevation in intracellular Ca(2+) monitored with Fura-2, and a significant increase in intramitochondrial oxidation of dihydrorhodamine 123, probably associated with transient increase of mitochondrial permeability, cytochrome c release, nuclear translocation of NF kappa B, and transcriptional activation of the oncogene p53. Interruption of any of these steps by specific antagonists prevented neurite pruning and programmed cell death.