Induced pluripotent stem cells (iPSCs) are obtained by reprogramming differentiated cells through forced expression of four embryonic transcription factors. The discovery of this technology, able to transform a differentiated cell into a pluripotent cell, has profoundly shifted the paradigm of the concept of cell identity, since it is now possible to obtain in vitro any cell type from an initial sample of skin or blood cells from a healthy volunteer or patient. Applications of iPSCs are exceedingly large, and comprise the in vitro modeling of normal or pathological tissues, including for massive drug screening. They also open new therapeutic avenues in the field of regenerative medicine.

Islet transplantation has set the ground for diabetes cell therapy and is still undergoing various developments that might improve clinical outcomes. Alternative sources for β-cell replacement strategies are now led by human pluripotent stem cells that demonstrate near-normal β-cell features after in vitro differentiation and which can reverse diabetes in mice. Yet, their propensity for tumor formation is still unresolved. The adult pancreas is suggested as a reservoir of facultative progenitors that could represent adequate candidates for β-cell engineering, either in vivo through pharmacological treatment or after expansion in culture. This review focuses on the latest developments in protocols aiming at de novo production of functional β cells.

Glioblastoma (GBM) is associated with a poor prognosis. This review will discuss different directions of treatment, mostly regarding immunotherapies and combinatorial approaches.

Immunosenescence is a progressive deterioration of the immune system with ageing. A multifactorial condition, including multimorbidities and environmental factors in the elderly, increases the frailty risks. Some infection and nutritional factors contribute to the onset of decline of response to infection. The epithelial barrier is the front line against infection. The renewal capacity of hematopoietic stem cells is reduced and provide in turn decrease of immune cells like lymphocytes, antigen-presenting dendritic cells, and phagocytes. The cellular immunity decreases considering the low cytotoxicity of natural killer. The impairment of dendritic cells alters both non-adaptive and humoral immunities. The reduction of antibody producing B-cells alters humoral production and the diversity of immunoglobulins and their affinity. Somme evidence suggests that retained function of both innate and acquired immunity in the elderly is correlated with health status. CMV might play a part in the process of immunosenescence. CMV status is included in the immune risk profile. Some factors like nutritional status and inflammatory biomarkers should be added to define a immune risk profile in the elderly.

Meningococcal vaccines in france. In France in 2015, several vaccines against invasive meningococcal disease (IMD) are available: non-conjugated polysaccharide vaccines (bivalent AC and tetravalent ACYW135) conjugate vaccines (monovalent A monovalent C and quadrivalent ACYW135) and a novel multicomponent meningococcal B vaccine. These vaccines have a very satisfactory safety profile. Currently in France, universal vaccination against serogroup C meningococcal disease is recommended for all infants at the age of 12 months with catch up till the age of 24 years. Vaccination against IMD B and C are also recommended to persons with specific individual risk factors (mainly asplenia, complement deficiency, hematopoietic stem cells) or travel in endemic areas. Despite recommendations, vaccination coverage remains below recommended levels in most of the targeted populations.

Originator GCSF (Neupogen) has been used to mobilize progenitor stem cells and treat therapy-induced neutropenia in Canadian stem cell transplant settings for years. Although its benefit is not in question, viable alternatives are available. Biosimilar GCSF (Zarzio) is widely in use in Europe since 2009 and was recently approved in the U.S.for the same five indications as Neupogen. Zarzio is reported as safe, equally efficacious, more accessible and cost effective without negatively impacting patient outcomes. This paper summarizes the supporting evidence.

A defining characteristic of the brain is its remarkable capacity to undergo activity-dependent functional and structural remodelling via mechanisms of plasticity that form the basis of our capacity to encode and retain memories. The prevailing model of how our brain stores new information about relationships between events or new abstract constructs suggests it resides in activity-driven modifications of synaptic strength and remodelling of neural networks brought about by cellular and molecular changes within the neurons activated during learning. To date, the idea that a form of activity-dependent synaptic plasticity known as long-term potentiation, or LTP, and the associated synaptic growth play a central role in the laying down of memories has received considerable support. Beyond this mechanism of plasticity at the synapse, adult neurogenesis, i.e. the birth and growth of new neurons, is another form of neural plasticity that occurs continuously in defined brain regions such as the dentate gyrus of the hippocampus. Here, based on work in the hippocampus, we review the processes and mechanisms of the generation and selection of new neurons in the adult brain and the accumulating evidence that supports the idea that this form of neural plasticity is essential to store and lead to retrievable hippocampal-dependent memories.

Traumatic Brain Injury (TBI) is a well-known public health problem worldwide and is a leading cause of death and disability, particularly in young adults. Besides neurological and psychiatric issues, pituitary dysfunction can also occur after TBI, in the acute or chronic phase. The exact prevalence of post-traumatic hypopituitarism is difficult to assess due to the wide heterogeneity of published studies and bias in interpretation of hormonal test results in this specific population. Predictive factors for hypopituitarism have been proposed and are helpful for the screening. The pathophysiology of pituitary dysfunction after TBI is not well understood but the vascular hypothesis is privileged. Activation of pituitary stem/progenitor cells is probably involved in the recovery of pituitary functions. Those cells also play a role in the induction of pituitary tumors, highlighting their crucial place in pituitary conditions. This review updates the current data related to anterior pituitary dysfunction after TBI and discusses the bias and difficulties encountered in its diagnosis.

Understanding adaptive signaling pathways in response to chemotherapy is one of the main challenges of cancer treatment. Activated in response to DNA damage, cell cycle and mitotic checkpoints activate the p53-p21 and p16-Rb pathways and induce apoptosis or senescence. Since senescent cells survive and produce a secretome that influences neighbouring cells, it is not particularly clear whether these responses are equivalent and if tumor cells escape these two suppressive pathways to the same extent. Predicting escape is also complicated by the fact that cancer cells adapt to treatments by activating the epithelial-mesenchymal transition and by producing clones with cancer-initiating cells features. Dedifferentiation pathways used in stressful conditions reconstitute dividing and sometimes more aggressive populations in response to chemotherapy. These observations illustrate the importance of tumor heterogeneity and the adaptation capacities of different intra-tumoral subclones. Depending on their oncogenic profile, on their localisation within the tumor and on their interaction with stromal cells, these subclones are expected to have different responses and adaptation capacities to chemotherapy. A complete eradication will certainly rely on combination therapies that can kill at the same time the bulk of the sensitive tumor but can also prevent plasticity and the generation of persistent clones.

The pathophysiological mechanisms of tendinopathies integrate various intrinsic and extrinsic factors. Classic "passive" therapeutics have a limited action. Because of a better pathophysiological understanding of tendinopathies, more recent treatments (injections of various compounds, infiltrations of platelet-rich plasma, stem cells) would lead to a long-term healing. In case of failure of conservative managements and depending on the anatomical site, a surgical approach may be considered.

The status of the human embryo has always be a subject of philosophical and theological thoughts with major social consequences, but, until the 19th century, it has been mainly an abstraction. The arrival of the human embryo in vitro, materialized by Louise Brown's birth in 1978 and above all by the supernumerary embryos produced by the Australian team of Trounson and Wood following the introduction of ovarian stimulation, will turn theoretical thoughts into a reality. Nobody may ignore the hidden intentions behind the debate, as to recognise a status to a few days old embryo will immediately have a major impact on the status of a few weeks old foetus and therefore on the abortion rights. We will see that the embryo status, essentially based as well on a vision on the good and evil as on social order, cannot be based on a scientific analysis of the reproduction process but comes from a society's choice, by essence " arbitrary " and always disputable. This does not preclude the collectivity right and legitimacy to give a precise status and it is remarkable to observe the law is careful not to specify which status to give to the human embryo. It is more thru handling procedures and functioning rules that the law designed the embryo position, neither with a status of a person, nor of a thing. It nevertheless remains true that there is a constant risk that the legislation gives the embryo a status that would call into question it's unique characteristic of early reproductive stage, jeopardizing at once the hard-won reproductive freedom (reproductive choice) as well as freedom of research on embryonic stem cells, one of the most promising field of medical research.

Radiation therapy is a cornerstone of head and neck cancer management. Technological improvements in recent years in radiation therapy, with intensity-modulated techniques, reinforce even more its role. However, both local and locoregional relapses are still observed. Understanding biological mechanisms of treatment resistance is a topic of major interest. From the cancer cell itself, its ability to repair and proliferate, its microenvironment and oxygenation conditions, migratory and invasive capacity, to biological parameters related to the patient, there are many mechanisms involving radiosensitivity and/or radioresistance of head and neck cancer. The present study explores the main biological mechanisms involved in radiation resistance of head and neck cancer, and describes promising therapeutic approaches.

Recent evidences suggest that many types of cancers contain a cell population presenting stem cell properties. While the great majority of tumor cells are destined to differentiate, and eventually stop dividing, only a minority population of cells, termed cancer stem cells (CSCs), possesses extensive self-renewal capability and can recapitulate tumor pathophysiology in an immune-compromised animal model. Tumor initiating cells have been identified and isolated in many tumor types including brain, colon and prostate. They are virtually resistant to radiation and may contribute to treatment resistance and recurrence. Therefore, therapies specifically targeting CSCs will likely be needed for complete tumor eradication. The present study reviews published reports identifying the mechanisms of radioresistance of CSCs and potential targets based on the pathways of self-renewal. Further elucidation of pathways that regulate CSCs may provide insights into the development of novel innovative therapies.

Development and repair of the nervous system are based on the existence of neural stem cells (NSCs) able to generate neurons and glial cells. Among the mechanisms that are involved in the control of embryo or adult NSCs, the Notch signalling plays a major role. In embryo, the pathway participates in the maintenance of NSCs during all steps of development of the central nervous system which starts with the production of neurons also called neurogenesis and continues with gliogenesis giving rise to astrocytes and oligodendrocytes. During the postnatal and adult period, Notch signalling is still present in the major neurogenic areas, the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampus. In these regions, Notch maintains NSC quiescence, contributes to the heterogeneity of these cells and displays pleiotropic effects during the regeneration process occurring after a lesion.