Thanks to the Internet, we can now have access to more information about spinal cord repair. Spinal cord injured (SCI) patients request more information and hospitals offer specific spinal cord repair medical consultations.

Cell therapy is already a clinical reality, having restored function to postinfarct akinetic myocardial scars. Ongoing trials are testing skeletal myoblasts in patients with chronic left ventricular dysfunction, and bone marrow-derived cells are being tried in patients with acute myocardial infarction undergoing concomitant percutaneous revascularization by angioplasty and stenting. While these procedures appear to be safe, their efficacy is uncertain. Indeed, the enthusiasm generated by the first phase I studies has been tempered by the less successful outcomes of recently published randomised controlled phase II trials. At least these studies have the merit of highlighting two major issues--the modest efficiency of cell transfer and the high rate of posttransplantation cell death--which need to be addressed if cell therapy is to hold its promise. Furthermore, it is becoming clear that the plasticity of adult somatic cells is likely to be much more limited than initially thought, and that the generation of new cardiomyocytes capable of ensuring true myocardial regeneration is still elusive. So far the documented effects of cell therapy are mainly due to aparacrine signaling action on the extracellular matrix, angiogenesis, or even recruitment of endogenous cardiac stem cells. Neither skeletal myoblasts nor bone marrow-derived cells meet the criteria required for true myocardial regeneration, i.e., electrical coupling between donor and recipient cells, leading to the formation of a syncytium and allowing the graft to beat in synchrony with the remainder of the heart and, thus, to effectively contribute to its pump function. We must therefore continue to explore other paths, notably using embryonic stem cells. If appropriately precommitted towards a cardiac lineage, these cells can diferentiate into cardiomyocytes following engraftment into postinfarct scars, leading to improved left ventricular function. Although several hurdles stand in the way of routine clinical applications, there are serious reasons for hoping that these cells will eventually provide an effective means of repairing diseased myocardial tissue.

Critical leg ischemia (CLI) remains a major cause of mortality and morbidity (amputation), and its treatment is a major challenge. Cell therapy designed to stimulate angiogenesis is being evaluated in this setting. Several phase III trials have demonstrated that it is safe and feasible to use autologous bone marrow mononuclear cells or peripheral mononuclear cells harvested after G-CSF stimulation. Three trials with more than 40 patients have been performed in France, and more than 700 patients have been treated worldwide, usually in non controlled trials. The main problems encountered with cell therapy in CLI are not only the need to demonstrate its efficacy and safety, but also to identify the patient categories most likely to benefit. The results of randomized trials, and especially the French BALI trial, are eagerly awaited to confirm that this approach is really beneficial. Afew trials have also been performed in Buerger's disease. Another exciting possibility is to create artificial vessels in vitro for subsequent grafting in patients with no available venous grafts. Several teams are also testing allogeneic stem cells and autologous progenitor endothelial cells for the treatment of peripheral artery disease but they are encountering significant hurdles.

The discovery of circulating endothelial progenitor cells (EPCs) in adult peripheral blood has opened up many exciting possibilities in vascular biology. Several studies have confirmed the existence of EPCs, as well as their bone marrow origin and their ability to integrate into vascular structures at sites of neoangiogenesis. EPCs appear to be naturally involved in the prevention of ischemia by participating directly in the vascularization process. Given their tropism for sites of neoangiogenesis, EPCs have clear therapeutic potential for treating ischemic diseases. If associated with other cell therapy products, they could improve tissue regeneration by promoting graft vascularization. However, the use of EPCs as a cell therapy product is limited by their rarity in peripheral blood. Cord blood contains many more EPCs, which are functional and can be expanded in culture. Their clinical use will require expansion in strictly controlled conditions and rigorous validation in preclinical models. EPCs could also serve as a quality markerforfrozen cord blood, showing the presence of non hematopoietic stem cells.

Medicine will be faced with a major challenge in coming years, namely how to treat for tissue dysfunction due to disease and aging There are two basic options: drug therapy and cell therapy. Stem cells have been the subject of intense speculation and controversy for several years, as they open up radically new therapeutic possibilities. Classical drugs can only smoothen consequences of tissue dysfunction, whereas cell therapy has the potential to restore tissue function by providing fresh cells. Cell therapy is totally different from organ transplantation, which can only benefit a limited number of patients. The use of the generic term "stem cells" to designate a whole variety of cell types that are present throughout life, is a source of confusion and ambiguity. It will take years of cognitive research to unravel the molecular mechanisms that govern a stem cell's multi- or totipotent status before we can fully exploit this therapeutic tool to the full. The younger a stem cell the greater its potential and, probably, the more durable its benefits, but the use of embryonic stem cells raises ethical issues. The redundancy or equivalence of diferent categories of cells is another source of controversy, yet researchers must be able to study stem cells in all their diversity, as complementary rather than competitive alternatives, in an acceptable ethical and regulatory environment. We briefly describe the three types of stem cells: pluripotent embryonic stem cells, fetal and adult stem cells, and pluripotent reprogrammed adult somatic cells. Only the former two categories have physiological functions: the first gives rise to tissues and organs while the second maintains tissue function during adulthood

There is less than three years, the reprogramming of adult cells in induced pluripotent stem cells (iPS cells) has been added to the techniques producing natural or manufactured embryonic cells. Easier to obtain than these last, the human iPS cells are ethically irreproachable. They allow the study of many disorders at the cellular level and put at the disposal of pharmacologists a material of an exceptional interest. The improvement of the quality of their reprogramming is the object of active search all over the world. It is not utopian to hope that the iPS cells will quickly take a choice place in human cellular therapy.

Because of their self-renewal and pluripotency properties, human embryonic stem cells (hES) receive a marked attention from scientists and clinicians for regenerative medicine. The most recent application of hES cells may however reside in their use as a tool in drug development. The currently available cellular models for preclinical testing consist in primary and immortalized cells that display limitations in terms of available amount and likeliness to their in vivo counterparts, respectively. hES cells have the potential to revolutionize drug discovery by providing a physiological model for any human cell type in the desired amount for the earliest steps of drug development, notably for pharmacological, metabolic and toxicity evaluation. This new generation of model may contribute to reduce, refine or replace animal testing and decrease drug attrition.

We report the occurrence of a cerebral toxoplasmosis 52 days after a non-myeloablative allogeneic stem cell transplantation as treatment for acute myeloid leukemia.

Corticosteroids have been used for the past 20-30 years to prevent lethal consequences of pulmonary and cerebral disorders linked to prematurity. However, many data suggest a low risk-benefit ratio, and the long-term emergence of adverse neurodevelopmental outcomes objectivated by RMN studies. Although multiple mechanisms have been proposed to explain GCs effects on brain development, none has clearly emerged so far. A breakthrough study has been recently published, which identified the sonic hedgehog (Shh) signaling pathway as the target of Gcs action. Shh is a crucial regulator of brain development and neural stem/progenitor cells, and GCs suppress Shh-induced proliferation of cerebellar progenitor cells ; Shh acts through the induction of the enzyme 11betaHSD2, which inactivates the GCs corticosterone and prednisolone, but not dexamethasone. These data should lead to the development of novel molecules (either GC or Shh agonists) both -efficient and neuroprotective.

Angiogenesis is central to cancer research. Recent progresses in understanding its mechanisms have enabled the development of therapies that inhibit this process. Many molecules have shown a synergistic effect in combination with irradiation in preclinical studies, and several are being tested in phase I or II. This effect could be explained by a transient normalization of tumor vasculature, leading to improve tumor oxygenation and thus greater radiosensitivity. Although promising, many questions remain about the dose, optimal sequences of the association.

Increasing studies show the central role of the tumor microenvironment, and more particularly the angiogenesis, in the response to anticancer treatment such as radiotherapy. Thus the association of angiogenesis inhibitors to radiotherapy is a strategy whose concept is based on several mechanisms of actions, such as the implication of the angiogenic factors in the control of tumor radiosensitivity, the regulation of the tumor radiosensitivity by that of the endothelial cells, the induction of hypoxia by the tumor angiogenesis, the induction of HIF-1alpha by irradiation and finally the importance of the angiogenic factors in the tumor stem cells survival, known to be radioresistant. These mechanisms will be detailed in this article as well as several clinical trials associating these inhibitors with radiotherapy.

The revision of the bioethics law of 2004 must occur in a five year's time. For this revision, the authorities decided to organize general states of bioethics and requested the production of contributions by the companies, institutions or associations. These texts tackle various subjects, like the Assisted Reproductive Technologies, research on the embryo and the stem cells and the banks of umbilical cord blood. Certain opinions converge, others differ, but all take part in the great debate which will take place at the time of the general conference.