Severe burned patients need definitive and efficient wound coverage. Outcome of massive burns has been improved by using cultured epithelial autografts (CEA). Despite fragility, percentages of success take, cost of treatment and long-term tendency to contracture, this surgical technique has been developed in few burn centres. First improvements were to combine CEA and dermis-like substitute. Cultured skin substitutes provide earlier skin closure and satisfying functional result. These methods have been used successfully in massive burns. Second improvement was to allow skin regeneration by using epidermal stem cells. Stem cells have capacity to differentiate into keratinocytes, to promote wound repair and to regenerate skin appendages. Human mesenchymal stem cells contribute to wound healing and were evaluated in cutaneous radiation syndrome. Skin regeneration and tissue engineering methods remain a complex challenge and offer the possibility of new treatment for injured and burned patients.

Several epidemiologic studies using the Surveillance, Epidemiology and End results program, have shown that the incidence of melanoma and of cutaneous lymphomas has clearly increased in the United States. Two independent groups have reported genome-wide association studies identifying variants associated to an increased risk of melanoma. Tumor stem cells were found to have an increased frequency when compared to previously reported studies, and also a greater plasticity. The Merkel cell polyoma virus seems rather ubiquitous, since it has been evidenced, without clonal integration, in several other types of cutaneous tumors, and even in healthy skin, with an increased frequency in photo-exposed skin and in immunodepressed patients. A recent study demonstrates for the first time a link between the exposure to pesticides and the occurrence of lymphomas. Another study has evidenced the association between topical treatments with steroids and the occurrence of lymphomas, especially cutaneous lymphomas. The risk is increased with the length of treatment and the potency of steroids. Adjuvant treatment of high-risk melanomas with alpha interferon does not achieve better results with the adjunction of a 4 weeks high-dose induction period, and development of autoantibodies is not significantly associated to an increased relapse free survival after correction of the time related biais. In contrast, the effect of interferon on relapse free survival, distant metastasis free survival and overall survival seems better in the subgroup of melanoma with primary ulceration. The development of new specific inhibitors of c-kit or BRAF is a great hope for the targeted treatment of peculiar groups of advanced melanomas. The main objectives of the new 2009-2013 Cancer Plan is to optimize the structuration of health organization in the field of oncology.

Allogeneic hematopoietic stem cell transplantation (alloHCT) is frequently used as treatment for patients with hematological malignancies. Its efficacy depends in part on the destruction of recipient tumor cells by donor immune cells contained in the graft (graft-versus-tumor effects), underlying the interest of studying donor immune recovery after alloHCT. Further, donor immune cells play an important role in the prevention and treatment of infections after alloHCT, and are the cause of graft-versus-host disease (GVHD). This article reviews the mechanisms of immune recovery after allogeneic hematopoietic cell transplantation (alloHCT), as well as techniques currently used to monitor immune function following alloHCT.

The aim of this study was to access average delays for novogeneration of myeloid and lymphoid cells after allogeneic bone marrow transplantation (BMT) outcome and factors affecting this organization. A prospective analysis over 2 years (01/01/07 to 31/12/08) enrolling 19 children treated with allogeneic intrafamilial bone marrow transplantation. Indications for bone marrow transplantation were: aplastic anemia (3 cases), bemoglobinopathies (9 cases), myelodysplastic syndrome (1 case) and primary immunodeficiency (6 cases). Different conditioning regiments were used according to the indication. The study of immune reconstitution was based on the quantitative determination of immunoglobulin and lymphocyte subpopulation. These tests were routinely requested to 1 month, 2 months, 3 months, 6 months, 9 months and 12 months. The average time of engraftment was 18 days (12-24). A rate of CD4+T lymphocytes>200/mm3 was provided within an average of 2,5 months (1-7). The average time to obtain CD8+T lymphocytes>200/mm3 was 2 months (1-5). The humoral immune reconstitution was made within an average of 2 months (1-4). A report of CD4+/CD8+T lymphocytes>I was obtained within 10 months and a half (1-24). Univaried analysis showed a correlation between the bone marrow sex matched and the faster reorganization of CD8+T cells (p=0.042). A quantity of CD34+>6 10(6)/kg was significantly associated with the recapture of a formula lymphocyte CD4+/CD8+T>1 (p=0.03) Immune recovery post bone marrow transplantation in children begins with myeloid lineage then lymphoid B then lymphoid T The inversion of the report CD4+/CD8+T lymphocytes, seems to be influenced by the high contain of CD34+cells in the graft as well as the type of conditioning.

Survival of lung transplant recipients is currently limited by the primary graft dysfunction, an acute phenomenon occurring within 72 hours after the transplantation, but also by the chronic rejection that appears more than one year later. IL-17 might be implicated in these two diseases. The heterotopic trachea transplantation in mice generates epithelial lesions mimicking the human pathology. Using this model, we show that IL-17 was crucially implicated in early, but not chronic lesions after transplantation. The main intragraft cellular sources of IL-17 are recipient-derived gammadelta T cells. However, the IL17-dependent lesions in our model are not mediated by a direct effect of IL-17 on donor-derived cells. Nevertheless, its inhibition protects CK-14+ basal epithelial stem cells that are known to be capable of renewing of the whole epithelium.

Paroxysmal nocturnal hemoglobinuria is a rare acquired clonal of the hematopoietic stem cell due to acquired mutation of the PIG-A gene. This results in the lack of two GPI-anchored membrane proteins involved in the inhibition of complement attack, thus explaining red cells hemolysis. The development of an anti-C5 monoclonal antibody (eculizumab) had profoundly modified the treatment of the the hemolytic form of the disease.

Activating mutations of the oncogene K-ras are found in one third of all human cancers. Much of our knowledge on K-ras signal transduction and its influence on tumor initiation and progression come from in vitro studies with cell lines. However, mouse models of human cancer allow a much more faithful recapitulation of the human disease, and the in vivo perspective is crucial for our understanding of neoplasia. In recent years, several new murine models for K-ras-induced tumorigenesis have been described. They allow new insights into the specific role that oncogenic K-ras proteins play in different solid tumors, and they permit the molecular dissection of the pathways that are initiated by somatic mutations in subsets of cells. Key advances have been made by the use of tissue-specific and inducible control of expression, which is achieved by the Cre/loxP technology or the tetracycline system. From these sophisticated models, a common picture emerges: the effects of K-ras on tumor initiation depend strongly on the cellular context, and different tissues vary in their susceptibility to K-ras transformation.

The epithelial-mesenchymal transition (EMT) is a morphogenetic program that converts epithelial into mesenchymal cells during the embryonic development. This mechanism is frequently reactivated during tumor progression and provides cells with motility and invasive capabilities favoring the metastatic dissemination from epithelial tumors. Various EMT-inducing transcription factors, such as the TWIST proteins, were also shown to inhibit oncogene-induced fail-safe programs (senescence and apoptosis), thereby promoting the progression from benign to malignant stages. Altogether, these observations suggest that EMT could play an important role in favoring both tumor development and metastatic dissemination.

Hematopoietic stem cell transplantation is the choice treatment of many hematopoietic disorders. However, there is still no related or HLA-matched unrelated donor for one-third of the patients. Cord blood, which contains a lot of hematopoietic progenitors immunologically naive, represents not only an interesting alternative as hematopoietic stem cell source but also allows more HLA incompatibilities than the other sources. Promising results in children lead to develop cord blood transplantation in adults first of all in hematopoietic malignancies (acute leukemias and lymphoid diseases) and in a second time, in non-malignant diseases such as aplastic anaemia. The main problems for the development of this new strategy in adults are the poor number of cells per unit, the delay for hematopoietic recovery in comparison with other hematopoietic stem cell sources and, consequently higher transplant related mortality. In order to improve the results in adults, new strategies emerged. Double cord blood transplantation, expansion methods and intra-bone injection of the graft will be reviewed here, as well as alternative transplantation strategies such as non-myeloablative conditioning.

Erythropoietin (EPO) is a glycoprotein hormone. This hormone is a growth factor for red blood cells precursors in the bone marrow. The decrease of oxygen partial pressure, a reduced number of erythrocytes caused by bleeding or excessive destruction, or increased tissues oxygen requirements lead to increased secretion of EPO. Its action takes place on bone marrow erythroblastic cells through specific receptors. EPO stimulates the proliferation of red cell precursors stem cells in the bone marrow, thus increasing their production in one to two weeks. The effectiveness of EPO at increasing haemoglobin and improving patients' quality of life has been demonstrated by several studies. However, its use in radiotherapy remains controversial. While tumour hypoxia caused by anaemia is a factor of radio resistance and thus a source of local failure, tumour expression of EPO receptors presents a significant risk for tumour progression and neo-angiogenesis, which would be increased during the administration of EPO. The purpose of this article is to answer the question: is there a place for EPO in combination with radiotherapy in the management of cancer?

The application of endothelial progenitor cells (EPC) cell-based therapy for regenerative medicine constitutes a promising therapeutic avenue for the treatment of cardiovascular diseases. Based on experimental studies demonstrating that bone marrow-, blood- or tissue-derived stem/progenitor cells improve the functional recovery after ischemia, clinical trials were initiated to address this new therapeutic concept. Although autolougous cell therapy was shown to improve perfusion and function of ischemic tissues, a number of issues remain to be adressed. The nature of the mobilizing, migratory and homing signals, and the mechanisms of action need to be identified and further defined. In addition, strategies to enhance homing, survival and therapeutic potential of EPC need to be developped to improve therapeutic effect and counteract EPC dysfunction in aged patients with cardiovascular risk factors. The present review article will discuss the mechanisms of action of different types of adult stem cells and several approaches to improve their therapeutic efficiency.

For several years, research for treatment of advanced ovarian cancer in first line or in relapse was made on the basis of two concepts. The first one is to improve the response rate by increasing the dose of chemotherapy delivered by high dose chemotherapy consolidation. The second concept is the development of an immunological antitumoral effect following allogeneic hematopoietic stem cells transplantation (HSC). The autologous HSC transplantation is required to first concept because of medullar toxicities induced by high dose chemotherapy. This therapeutic was widely studied in first line of advanced ovarian cancer. The recent phases III demonstrate an increase of the toxicity without efficacy improvement compared with the standard doses of chemotherapy. In relapse, the response rate is improved but an important toxicity is observed with low response duration. Evaluation of high dose of topotecan in association with the carboplatine is currently on going. Allogeneic HSC transplantation presents a potential interest because of immunogeneic control against tumour. However, the direct proof of immunotherapy efficacy on OC in a clinical study is still missing, toxicities should not be disregarded.

A new discipline was born and grew up over the last 4 decades of 20th century: Experimental Hematology. In addition to yield the concept of Stemness, a paradigm later applied for the other tissues than hematopoietic one, it provided the results allowing a preclinical development and a therapeutic exploitation. The concept of ex vivo expansion of hematopoietic cells for transplantation is directly issued from this knowledge. It enabled us to realize that a critical quantity of different sub-populations of stem and progenitor cells are necessary to obtain a rapid and sustained hematopoietic reconstitution. These principles, transposed to human cells (originating from: bone marrow, peripheral blood, cord blood) required some important technological innovations (conception of the specific media, recombinant technology of cytokine production...), to achieve, after several attempts, the first efficient clinical trials (at the moment for cells mobilized in peripheral blood). This goal remains to be achieved for cord blood cells too. The developments in this field as well as its actual state are the subjects of this review.

To review the main studies and the recent surgical procedures in tracheal reconstruction.

Mycosis fungoides during large cell transformation to lymphoma has a poor prognosis with mean survival of 36 months. Autologous stem cell transplantation is rarely proposed in this indication. We report the case of a young man still in complete remission for transformed mycosis fungoides 14 years after autologous stem cell transplantation.