The existence of a growth and regeneration cycle makes the hair follicle a true paradigm of tissue homeostasis. Analysis of about 9000 cycles led us to propose a stochastic model of human hair dynamics. The existence of hair cycles implies that stem cells must be cyclically activated and hair melanin unit has to be renewed. Using different markers, we were able to identify two distinct epithelial stem cell reservoirs, located in the upper and lower thirds of the anagen hair follicle outer root sheath. These two reservoirs fuse during the regression phase and individualize again in the new forming anagen hair follicle. Using a set of antibodies specific of melanocyte lineage and melanogenesis, pigmentation unit turnover was followed throughout the entire hair cycle. In the terminal anagen hair, active melanocytes were localized on top of the dermal papilla, while amelanotic melanocytes were identified in the upper third of the outer root sheath (ORS). Those amelanotic melanocytes located in upper ORS probably represented a melanocyte reservoir for successive hair generation, since at the induction of anagen phase, some melanocytes were committed to cell division and melanogenesis was turned on, but only in the nascent hair bulb, close to the dermal papilla.

To study time-scheduled regimens in the treatment of tumours by cytotoxic drugs delivered by IV injection, we propose a mathematical model of the action of a chemotherapy on the population of tumoral cells on the one hand, on a population of fast renewing healthy cells on the other hand. We chose for model parameter identification the treatment by oxaliplatin of Glasgow Osteosarcoma in mice.

The application of stem cell therapy to cure degenerative diseases offers immense possibilities, but the research in this field is the subject of ethical debates raised by the question of destructive research on early human embryos. Stem cells taken in the adult constitute an alternative to human embryonic stem cells, but our knowledge on totipotent or pluripotent cells is currently insufficient. Furthermore, many questions must be solved before selection and differentiation of these cells in a given cellular type can be controlled on a routine basis. What are the molecular characteristics of an adult stem cell? What are the mechanisms involved in cell reprogramming? Which signals control stem cell replication and differentiation? Basic research activities must be carried out in order to clarify all these points. In this context, the regeneration of vertebrate appendages provides a model for this type of research. The regeneration process is defined by both the morphological and functional reconstruction of a part of a living organism, which has previously been destroyed. But why are some vertebrates able to regenerate complex structures and others apparently not? Among most vertebrates, the capacity to regenerate is limited to some tissues. It is however possible to observe the regeneration of appendages (limb, tail, fin, jaw, etc.) among several amphibians and fish. This regeneration leads to re-forming of the amputated part with a complete restoration of its shape, segmentation and function. Why is the amputation of limbs not followed by regeneration in mammals and birds: absence of stem cells, absence of recruitment signals for these cells, or absence of signal receptivity? This review constitutes a report on the current understanding of the basis of on regeneration of legs in tetrapods and of fins in fish with an emphasis in the role of the nervous system in this process.

Systolic heart failure is mainly due to a decreased left ventricular systolic function after myocardial infarction. Despite significant improvements in medical management of heart failure, the prognostic remains poor, with a 5-years survival only of 30%.

The ability to identify, select and manipulate stem cells from tissues opens the way to regenerative medicine. In the field of hematopoiesis, our increasingly precise knowledge of the mechanisms of production and regulation of blood cells should permit in the near future the production of cells in sufficient quantity to be of interest for transfusion. Our present capacity to amplify hematopoietic stem cells and direct their differentiation towards the erythroid line is reviewed here. A procedure is described for the amplification of CD34 + hematopoietic stem cells of placental origin, based on the sequential use of specific combinations of growth factors in a given serum-free medium. Such conditions allowing the terminal maturation in vivo of large numbers of precursors produced ex vivo permit one to envisage important transfusion perspectives. A complementary source of red blood cells would in fact improve our transfusion capacity.

In order to effectively perceive the huge diversity of antigenic determinants to which it is confronted, the immune system uses referring internal images from self. The major histocompatibility complex constitutes the main reference to self, essential to the operating system of T and NK lymphocytes. It is involved in shaping the T operating repertoire in the thymus, where each differentiating thymocyte, with its TCR interacting with the MHC-peptide self complexes exposed by thymic presenting cells, should answer to both questions: Is it really necessary (positive selection) Is not dangerous (negative selection)? Once in periphery, naive T lymphocytes will undergo an homeostatic control helping their survival through the same contacts between TCR and MHC-peptide self complex than those which allowed the thymic positive selection. In a more hypothetic way, it is possible that contact between a T lymphocyte and the rare foreign MHC-peptide complexes spread at the surface of antigen presenting cell, is not sufficient to initiate its activation. Some arguments exist to involve the MHC-peptide self complexes themselves in the activation process.Finally, the MHC also constitutes a quality referential for the NK lymphocytes. When a somatic cell, infected by a virus or transformed, repress the expression of one or more of its class I HLA alleles, this absence of the self is perceived by the NK lymphocytes which proceed to its elimination through cytolysis. This disposition to sanction the non-self is also used for therapeutic purpose in the case of a non HLA identical allogenic hematopoïetic stem cells graft.

Recognition of the importance of immune cells present in a hematopoietic graft has resulted in a significant change in the perception of allogeneic hematopoietic transplantation. Such a transplant modality is now perceived has a very efficient form of adoptive allogeneic immunotherapy unfortunately associated with significant toxicity.

Our increasing knowledge of the mechanisms of blood regulation allows us to envisage the production of cells in quantities sufficient enough to have transfusional interest. We present the state of the art on our capacity to amplify hematopoietic stem cells (HSC) and to force their differentiation into the erythroid lineage. We describe the difficulties met ex vivo for simultaneously reaching a very high level of expansion to have meaningful transfusional interests and obtaining a complete terminal maturation up to enucleation. We describe here a procedure for massively amplifying HSC from human cord blood to produce erythroblastic precursors able to differentiate in vivo into mature red cells after infusion. Although we do not suggest to replace classical blood transfusion, we consider that this approach may become complementary.

In France, the necessity of managing sanitary risks associated with blood transfusion has induced a strong medicalization of blood collection. Practicing this activity of transfusion medicine confronts the professional with problems which the medical science is not sufficient to answer: curbs and motivations for donating, seasonal and geographic fluctuations in blood collection, sense of pre-donation interview, individual or collective contestings of guidelines for blood collection. From recent sociological works on donation in France, especially on blood donation, this paper suggests reporting the complexity of blood donation thought process and the necessity to refer to human and social sciences to approach it in a best way. Understanding the gift should help professionals to communicate not only on the promotion of blood donation, but also on the risk and its management.

Until recently, adults stem cells, defined by their self-renewal and differentiation abilities, were thought to be tissue-specific. This concept has been challenged by bone marrow transplantation experiments in mice, demonstrating generation of cells of different phenotype after transplantation of marrow or muscle cells. The term "plasticity" has been coined to explain this phenomenon which could be due to the persistence in adult tissues, of stem cells with multidifferentiation ability or to the "transdifferentiation" ability of some adult cells committed to differentiation, under the influence of unknown environmental cues. The relationship of the cells at the origin of the stem cells plasticity with a new type of mesodermal cell designed under the term of "multipotent adult progenitor cell" (MAPC) remains to be determined. The discovery of this latter is a major advance in this field as the MAPC have isolated from the adult bone marrow and presents certain characteristics of embryonic stem cells with the demonstration of their totipotency towards many tissues, including hematopoiesis. The discovery of the adult stem cell plasticity phenomenon in general, represents a major change in our concepts of stem and developmental biology and possibly the basis for the development of future cell therapy protocols.

In rodents, bone marrow contains stem cells that have the potentiality to differentiate into mesodermal and non-mesodermal cells, both in vitro and in vivo. These cells can populate a wide panel of organs such as the liver, the brain, the lungs, the heart.... They appropriately differentiate according to the environment in which they migrate and are known to assume specific functions. Even in adult animals, these cells can migrate and differentiate. Such a potentiality suggests exciting therapeutic outcomes. Brain lesions could benefit of such techniques. These experimental protocols should be precisely controlled before their use in medicine in order to solve problems that still remain such as the permeability of the hemato-encephalic barrier, the integration of differentiated grafted cells into local functional neural networks.

Since 1990, specific documentation is established between the immunohematology laboratory of the French EFS Lorraine-Champagne and the marrow transplantation unit of the CHU of Nancy, for patients undergoing hematopoietic stem cells transplantation. These documents and the standardization of the immunohematologic follow-up of those patients, have contributed to the improvement of the transfusion safety.

In addition to its role in hematopoiesis, bone marrow appears to be a reservoir of stem cells that can differentiate into components of vessel wall. Upon stimulation by factors such as tissue ischemia, bone marrow stem cells can enter into circulating blood, and incorporate into areas of vascular development. Animal models suggest that bone marrow is a cellular source for tissue repair and/or regeneration. Data from humans, and clinical trials using bone marrow stem cells for the treatment of chronic ischemia in limbs and myocardium, support the view that stem cells may represent a new tool for the treatment of ischemia.