Given the current developments of therapeutic strategies in the field of neurodegenerative disorders, exact diagnosis, especially at an early stage, is becoming increasingly crucial for optimal patient care. Importantly, the new diagnosis criteria of dementia include functional imagery as well as CSF biomarkers. Proteomics investigations of these CSF biomarkers have produced quite promising results. The interest of CSF analysis resides in the anatomical and pathophysiological characteristics of this fluid. In this article, we will review current proteomics investigations of CSF which have led to the discovery and validation of biomarkers, mainly in the field of neurodegenerative disorders in Alzheimer's disease.

We report an atypical feature of neuromeningeal cryptococcosis presenting as spinal cystic arachnoiditis and cerebellar cryptococcoma in a child treated for pontine glioma.

In mammalian species, gametes are issued from primordial germ cells (PGC). PGC represent a small cell population, appearing during early embryo development. Gametes production is essential for fertilization process and therefore the establishment of the next generation. The gametes are different from somatic cells because they have a haploid number of chromosomes that are normally generated during the cellular division known as meiosis. The embryonic stem cells that appear at the fifth or sixth day within the blastocyst inner cellular mass are pluripotent cells. Therefore, they can differentiate into the three cellular lineages, somatic as well as germinal. It is well established that the mouse embryonic stem cells can be differentiated in vitro into primordial germinal cells. These cells enter into meiosis forming male or female gametes. In vitro production of gametes by induction from embryonic stem cells has become a very important aspect of the actual research constituting an alternative tool for infertility treatment.

Among patients which develop glioblastoma multiform (GBM), recurrence is the rule despite continuous progress in surgery, radiotherapy and chemotherapy. In the adult, GBM is the most frequent and most aggressive tumour of the Central Nervous System. A better understanding of the mechanisms by which these tumours relapse could promote the use of preventive therapy and could increase patients' survival. GBM stem cells have been recently described and it was demonstrated that they are specifically implied in the experimental tumorigenesis. It is thus very attractive to speculate on a possible relationship between these GBM stem cells and the neural stem cells which are persisting in the neurogenic zones of the adult brain. In this review, we formulate and discuss the hypothesis by which, in a patient with GBM, malignant stem cells might be present in the neurogenic zones, away from the tumour mass. This hypothesis could explain the tumour relapse observed after the first treatments.

Cord blood transplantation is used to treat patients with malignant and nonmalignant hematopoietic diseases. This study assessed the feasibility of collecting cord blood for eventual transplantation to a sibling with such a disease.

This study's objective was to evaluate the tolerance and safety of a new ophthalmic solution based on ReGeneraTing agent (RGTA) technology in a pilot noncontrolled exploration on compassion use for corneal ulcers and severe chronic dystrophies resistant to the usual treatments.

Chronic-granulomatous disease (CGD) is a rare inherited primary immunodeficiency syndrome caused by a defective oxidative metabolism of phagocytic cells. Dysfunction of the membranous NADPH oxidase complex leads to a greatly increased susceptibility to severe fungal and bacterial infections, early in childhood. The most severe and frequent type of GCD is the X-linked transmitted form caused by mutations in the CYBB gene encoding the redox element of the oxidase complex, gp91phox or Nox2. However, very rare autosomal recessive CGD affecting other oxidase components than Nox2 are characterized by mild-clinical manifestations that could appear later at the adult age. Long-term antibiotic prophylaxis is essential to prevent infections associated with CGD, but approaches based on hematopoietic stem-cell transplantation and gene therapy offer valuable hope in a near future.

Apoptosis represents a particular form of programmed cell death which appears in all the damaged cells and potentially hazardous. It plays a crucial role in the development of multicellular organisms by assuring and maintaining the cellular homeostasis. Thus, apoptosis intervenes not only in the normal process of organisms' development but also in immune defence and in cancerous cells detection. Indeed, any blockage in the program of the apoptotic machinery would be responsible of some neurodegenerative and auto-immune diseases and could play a crucial role in different steps of carcinogenesis. Some researchers were very interested in studying apoptosis in hematopoietic stem cells CD34+ which could be intended to be reinfused to patients suffering from malignant diseases. They have noted that kinetic study of apoptosis of the hematopoietic stem cells CD34+ after the process of cryoconservation is also necessary. Such study permits to quantify the real and exact number of the viable hematopoietic stem cells CD34+ and therefore to eliminate such risk which would be associated with the reinfusion of apoptotic cells to patients. In this paper, we describe our contribution to hematopoietic stem cells CD34+ study by flow cytometry before and after cryopreservation by using annexin V as a specific probe allowing detection of phosphatidyl serine, one of the major features of apoptosis. But, we have noted a pronounced induction of apoptosis in peripheral mobilized blood compared to cytapheresis (after cryopreservation: 29.79% of apoptotic HSC CD34+ in peripheral mobilized blood but only 11.67% apoptotic HSC CD34+ in cytapheresis). Besides, we have noticed that hematopoietic stem cells CD34+ have had a statute of viability better than other mononuclear cells. These results put in value the reliability, the simplicity and the efficiency of flow cytometry for the analysis of apoptosis in hematopoietic stem cells CD34+ by following the intensity of fluorescence of annexin V.

We assessed over 15 months the distribution of total coliforms concentrations of Escherichia coli, Enterococci, Pseudomonas aeruginosa, Salmonella and Staphylococcus aureus in three monitoring points in the Etueffont landfill (Belfort, France). We selected the piezometer (PZ30) which is located downstream from the dump and two leachate collectors from the old dump and the new casing. The results showed that the leachate was free from both Salmonella and Staphylococcus aureus. The absence of Salmonella was most likely due to the small occupation of the landfill environment by vertebrates, especially rodents, birds and reptiles, which are known to be principal vectors of Salmonella. S. aureu, is generally hosted on skins and mucus of animals. The mean densities of E. coli and Enterococcus in the leachates were low. In contrast, P. aeruginosa abundance was high and closely related to precipitations. Coliform bacteria concentrations in the leachate averaged UFC.100 CFU x ml(-1). In the contaminated groundwaters, the coliforms, E. coli and Enterococci were always present at concentrations 10 to 100 fold higher than those reported from septic tank effluents. P. aeruginosa concentrations were low (mean: 11 CFU.100 ml(-1)) and inferior to those quoted in the leachate. This may be explained by the anoxic conditions which prevailed in the shistous aquifer. The absence of Salmonella in groundwaters may be due to its sensitivity to disinfectants and that of S. aureus linked to the fact that it is not a common host of the human intestine. Finally, our study clearly indicates the role played by E. coli and Enterococci as biomarkers of recent faecal contamination.

Skin and cornea both feature an epithelium firmly anchored to its underlying connective compartment: dermis for skin and stroma for cornea. A breakthrough in tissue engineering occurred in 1975 when skin stem cells were successfully amplified in culture by Rheinwald and Green. Since 1981, they are used in the clinical arena as cultured epidermal autografts for the treatment of patients with extensive burns. A similar technique has been later adapted to the amplification of limbal-epithelial cells. The basal layer of the limbal epithelium is located in a transitional zone between the cornea and the conjunctiva and contains the stem cell population of the corneal epithelium called limbal-stem cells (LSC). These cells maintain the proper renewal of the corneal epithelium by generating transit-amplifying cells that migrate from the basal layer of the limbus towards the basal layer of the cornea. Tissue-engineering protocols enable the reconstruction of three-dimensional (3D) complex tissues comprising both an epithelium and its underlying connective tissue. Our in vitro reconstruction model is based on the combined use of cells and of a natural collagen-based biodegradable polymer to produce the connective-tissue compartment. This porous substrate acts as a scaffold for fibroblasts, thereby, producing a living dermal/stromal equivalent, which once epithelialized results into a reconstructed skin/hemicornea. This paper presents the reconstruction of surface epithelia for the treatment of pathological conditions of skin and cornea and the development of 3D tissue-engineered substitutes based on a collagen-GAG-chitosan matrix for the regeneration of skin and cornea.

Porphyrias are a group of disorders due to a genetic deficiency in one of the heme biosynthetic pathway enzymes. Congenital erythropoietic porphyria (CEP) is the most severe type characterized by a deficiency in uroporphyrinogen III synthase (UROS) activity. Bone marrow transplantation represents a curative treatment for patients, as long as human leucocyte antigen-compatible donor is available. We used a recently obtained murine model to check the feasibility of gene therapy in this disease. Lentivirus-mediated transfer of the human UROS cDNA into hematopoietic stem cells (HSCs) from Uros(mut 248) mice resulted in a complete and long-term enzymatic, metabolic and phenotypic correction of the disease, favored by a survival advantage of corrected red blood cells. These results demonstrate for the first time that the cure of this mouse model of CEP at moderate transduction level supports the proof of concept of a gene therapy in this disease by transplantation of genetically modified HSCs.

Prospects of ex vivo cutaneous gene therapy rely on stable corrective gene transfer in epidermal stem cells followed by engraftment of corrected cells in patients. In the case of cancer prone genodermatoses, such as xeroderma pigmentosum, cells that received the corrective gene must be selected. However, this step is potentially harmful and can increase risks of immune rejection of grafts. These obstacles have recently been overcome thanks to the labeling of genetically modified stem cells using a small epidermal protein naturally absent in stem cells. This approach was shown to be respectful of the fate of epidermal stem cells that retained full growth and differentiation capacities, as well as their potential to regenerate normal human skin when grafted in a mouse model in the long term. These progresses now open realistic avenues towards ex vivo cutaneous gene therapy of cancer prone genodermatoses such as xeroderma pigmentosum. However, major technical improvements are still necessary to preserve skin appendages which would contribute to aesthetic features and comfort of patients.

The AHA has released its annual selection of the 10 top major advances in heart disease and stroke research for 2007. This list is very interesting. It contains papers on genetics which present the newly introduced genome-wide association studies of different common diseases, including coronary artery disease. The results of investigations carried out on cardiomyocytes derived from adult mouse spermatogonial stem-cells are mentioned. The value of angioplasty in chronic stable coronary artery disease is reassessed as is the need for mouth to mouth ventilation in resuscitation manoeuvres for cardiac arrest. The effectiveness and safety of drug-eluting stents in routine clinical practice is demonstrated and the merit of bivaluridin for the treatment of patients with a STEMI infarct is described. The improvement in quality of care provided by a statewide system for coronary revascularisation is outlined. Finally, two papers are devoted to epidemiological issues: one demonstrates that a reduced sodium intake lowers not only blood pressure, but also the risk of clinical cardiovascular disease outcomes; the second stresses that hypertension and prehypertension are often undiagnosed in the pediatric population.

Human embryonic stem cells (hESC) are obtained from the inner cell mass from the early embryo at blastocyste stage. Derived in cell lines for the first time in 1998, they can be maintained in culture in an undifferentiated state indefinitely under certain conditions. Two essential properties characterize hESC: pluripotency and self-renewal. Pluripotency is convey by the expression of specific transcription factors such as OCT4 and NANOG, and is under the control of growth factors such as IGF2 and FGFb. Markers used to characterize these cells include surface antigens, notably SSEA-3 and SSEA-4, and nuclear markers such as OCT4. HESC can differentiate into different cell types in vitro. They represent a unique and essential model for early human development research and for regenerative medicine. By their self-renewal capacity and their potential to differentiate into several cell types, hESC are an unlimited source of cells enabling to replace or restore lost or damaged cells in numerous diseases. Even if it is not conceivable today to use them in clinical practice for ethic and scientific reasons, it seems essential to explore the numerous potentialities of these cells. This knowledge might be relevant to handle adult stem cells in vitro and will be mandatory for a therapeutic use of hESC in the future.

Deciphering the mechanisms underlying skeletal muscle differentiation in mammals is an important challenge. Cell differentiation involves complex pathways regulated at both transcriptional and post-transcriptional levels. Recent observations have revealed the importance of small (20-25 base pairs) non-coding RNAs (microRNAs or miRNAs) that are expressed in both lower organisms and in mammals. miRNAs modulate gene expression by affecting mRNA translation or stability. In lower organisms, miRNAs are essential for cell differentiation during development; some miRNAs are involved in maintenance of the differentiated state. We have shown that miR-181, a microRNA that is strongly upregulated during differentiation, participates in establishing the muscle phenotype. Moreover, our results suggest that miR-181 downregulates the homeobox protein Hox-A11 (a repressor of the differentiation process), thus establishing a functional link between miR-181 and the complex process of mammalian skeletal muscle differentiation. Therefore, miRNAs can be involved in the establishment of a differentiated phenotype - even when they are not expressed in the corresponding fully differentiated tissue.

In the past few years, significant advances have been performed in the field of cell-based therapies. This concerns mainly regenerative medicine with the use of stem cells, as well as the modulation of immune responses. In order to modulate allogeneic immune responses after transplantation, we have developed a cell therapy approach based on the immunomodulatory properties of intravenous donor apoptotic cell infusion. In allogeneic hematopoietic cell transplantation settings, we reported that intravenous apoptotic leukocyte infusion, simultaneously to allogeneic bone marrow grafts, favors hematopoietic engraftment, prevents alloimmunization and delays graft-versus-host disease. Here, we review the different factors and cells implicated in the immunomodulatory properties of apoptotic cells. Then, we discuss the potential significance of such observations in transfusion practice.

Considering that there is a shortage of organ donor, the aim of tissue engineering is to develop substitutes for the replacement of wounded or diseased tissues. Autologous tissue is evidently a preferable transplant material for long-term graft persistence because of the unavoidable rejection reaction occuring against allogeneic transplant. For the production of such substitutes, it is essential to control the culture conditions for post-natal human stem cells. Furthermore, histological organization and functionality of reconstructed tissues must approach those of native organs. For self-renewing tissues such as skin and cornea, tissue engineering strategies must include the preservation of stem cells during the in vitro process as well as after grafting to ensure the long-term regeneration of the transplants. We described a tissue engineering method named the self-assembly approach allowing the production of autologous living organs from human cells without any exogenous biomaterial. This approach is based on the capacity of mesenchymal cells to create in vitro their own extracellular matrix and then reform a tissue. Thereafter, various techniques allow the reorganization of such tissues in more complex organ such as valve leaflets, blood vessels, skin or cornea. These tissues offer the hope of new alternatives for organ transplantation in the future. In this review, the importance of preserving stem cells during in vitro expansion and controlling cell differentiation as well as tissue organization to ensure quality and functionality of tissue-engineered organs will be discussed, while focusing on skin and cornea.

Ewing's tumour is the second most frequent primary tumour of bone. It is associated in 85% of cases with a specific and recurrent chromosome translocation, a t(11; 22)(q24; q12) which generates a fusion gene between the 5' part of EWS and the 3' part of FLI-1, a member of the ETS family. Less frequently, this gene fusion involves EWS and another member of the ETS family which can be: ERG, ETV1, E1AF or FEV depending on the cases. The EWS-ETS fusion is causative in the development of Ewing's tumour. Its mechanism of action mainly relies on the abnormal transcription regulation of key target genes which are involved in the regulation of cell cycle, signal transduction, migration. The cellular context within which EWS-FLI-1 exerts its oncogenic action is a long standing matter of debate. Recent data converge to suggest that the Ewing cell origin is a mesenchymal stem cell.