The insulin-sensitizing thiazolidinediones are effective drugs to achieve glycemic control in patients with type 2 diabetes. Results from preclinical studies have demonstrated that activation of PPAR-gamma inhibits primarily bone formation by diverting mesenchymal stem cells to the adipocytic rather than to the osteogenic lineage. In humans studies demonstrated accelerated bone loss, impaired bone mineral density as well as an increased fracture risk for thiazolidinedione users, mostly for women. As a consequence of these observations, clinicians have to carefully assess the fracture risk in patients with type 2 diabetes before starting a therapy with thiazolidinediones.

In esthetic dermatology, filling and laser treatments are two essential techniques. Several recent studies on calcium hydroxyapatite in filling treatments and facial volumetry, in esthetics, but also in HIV patients, have been published. It was also tested in accentuated melomental folds where it is superior to hyaluronic acid. In aging of the skin of the dorsal aspect of the hands, hyaluronic acid provides slightly better results than collagen. Filler rhinoplasty can correct minor deformations of the nose. Lipofilling is advantageous for linear scleroderma of the face, at least in the forehead region, and adipocyte stem cells may be a future solution for facial aging or lipoatrophy. The risk of local and/or general sarcoid reactions related to interferon in patients having undergone filling injections has been reported. In the field of laser treatment, fractionated photothermolysis has motivated much more research and seem particularly valuable in treating acne scars, aging of the dorsal aspect of the hands, and, more anecdotally, in colloid milium and pearly penile papules. Laser is also useful in preventing surgical scars where a mini-diode can also be used. For axillary hyperhidrosis, subdermic Nd-YAG laser competes with botulinum toxin, with longer-lasting results. Solutions are appearing for treatment of red or white striae cutis distensae. Intense pulsed light is the reference technique for poikiloderma of Civatte, and seems effective, with new devices, for melasma. However, inappropriately used by nonphysicians, IPL can cause serious ocular accidents; one case of uveitis has been reported.

JACIE, a European certification program for stem cell transplantation, has now been recognized by the French Health Authorities. It can be considered as an evaluation of professional practice, an activity that can be promoted by health centres. The present article has two aims: firstly, it describes the structure of the certification standard based on the relative structure of each of its components; secondly, it reports on the experience acquired by the Léon-Bérard cancer centre (Lyon-France) during the certification of its own stem cell transplantation program. The JACIE manual written in English is divided into three parts corresponding to the three processes identified. Part B describes the clinical haematopoietic stem cell transplantation program. Part C is dedicated to the collection of haematopoietic stem cells from blood and marrow. Finally, part D applies to the cell therapy laboratory in charge of cell preservation and the preparation of grafts for re-infusion. After the application has been submitted to the JACIE board, a date is set for an inspection visit. The cell therapy laboratory at Léon-Bérard cancer centre has already participated to a certified transplantation project of the Edouard-Herriot Hospital (Lyon public hospitals) [parts C and D of the certification]. The executive board proposed that the clinical haematology unit of the cancer centre also applied for JACIE certification. A multidisciplinary work group-combining document writing skills and a real capacity to convince and motivate clinical staff was formed. Secondly, a comprehensive collection of existing documents was issued and the clinical pathway of the patients was formalized so that no step of the graft process would be omitted. A physician from another hospital also tested the evaluation process with the organisation of a mock visit. He confirmed that everything was in good way and provided recommendations to improve the program. This huge preparation provided invaluable learning opportunities to the participants. After the final visit by JACIE inspectors, the cancer centre received four-year certification. The challenge is now to maintain this momentum for the next certifications and to better take into account the ethical and juridical constraints of haematopoietic stem cell transplantation.

Type 1 diabetes currently affects 15,000 patients in Switzerland with a rising incidence worldwide. Pancreas or islet of Langerhans transplantation are alternatives to intensive insulin treatment, which decreases long-term complications at the cost of an increase of severe hyoglycemia. Pancreas transplantation, indicated mainly to diabetic patients with simultaneous kidney transplantation, has a high success rate, but is accompanied by high morbidity due to general surgery. Islet transplantation, a cell-therapy for type 1 diabetes, is in full development. It is mainly indicated as islet transplant alone in patients suffering from brittle diabetes, and is associated with a very low risk due to minimally invasive technique, but a lower rate of long-term success. New potential sources of beta cell replacement are beta-cell lines, stem cells and xenotransplantation.

Human embryonic stem cells (hESC) are derived from the inner cell mass (ICM) of the human blastocyst at day 5 or 6 of the early embryo development. These cells display two cardinal features: they are able to differentiate into cell types from many if not all human tissue (pluripotency) and they proliferate strongly and indefinitely without senescence in vitro. Therefore, hESC are a source of choice for stem cells for regenerative medicine and are a reference model to study the biology of pluripotency. Since 2004, the French law (loi de Bioéthique) authorizes hESC research under certain conditions.

Injection of endothelial progenitor cells (EPC) expanded ex vivo has been shown to increase neovascularization in preclinical models of ischemia and in adult patients, but the precise origin and identity of the cell population responsible for these clinical benefits are controversial. Given the potential usefulness of EPC as a cell therapy product, their thorough characterization is of major importance. This review describes the two cell populations currently called EPC and the means to find differential phenotypic markers. We have shown that BMP2/4 are specific markers of late EPC and play a key role in EPC commitment and outgrowth during neovascularization. Several authors have attempted to expand EPC ex vivo in order to obtain a homogeneous cell therapy product. One possible mean of expanding EPC ex vivo is to activate the thrombin receptor PAR-1 with the specific peptide SFLLRN. Indeed, PAR-1 activation increases angiogenic properties of EPC through activation of SDF-1, angiopoietin and IL-8 pathways. This review summarizes the characterization of EPC and different methods of ex vivo expansion.

Intra-aortic haematopoiesis is a transient phenomenon, characterised by the emergence of Hematopoietic Stem Cells (HSC) from the ventral aortic endothelium through an endothelial cell (EC) to HSC lineage switch. HSC differentiation is followed by the colonization of definitive haematopoietic organs. Since intra-aortic haematopoiesis is born from EC of the aortic floor, we wondered how vascular integrity was maintained during hematopoietic production. We have used interspecific quail to chick grafts to study the aortic morphogenesis during hematopoiesis. We have demonstrated that: 1) before haematopoiesis, the aortic endothelium, originally entirely from splanchnic origin, was colonized by somitic EC, creating a new roof and sides derived from the somite, whereas the floor was contributed by splanchnopleural-derived EC. 2) As haematopoiesis proceeded, somite-derived EC colonized the aortic floor, where they settled underneath the HSC clusters. 3) After haematopoiesis, splanchnopleural ECs have disappeared from the aortic floor and have been replaced by somite-derived EC. At this stage, the whole aortic endothelium originated from somitic cells. 4) We have identified that the somite contributed to the vascular smooth muscle cells (VSMC). 5) Using grafts of either single quail dermomyotome or sclerotome in the chick, we showed that EC originated from the dermomyotome whereas the vascular smooth muscle cells originated from the sclerotome. Taken together, our results bring about new insights on aorta morphogenesis and the time-restricted production of HSCs.

The incidence of skin cancers is still on the rise despite information provided to the public and to cancer screening initiatives. We designed a 3D movie with the support of all Belgian university departments of dermatology. Looking at the impact of ultraviolet light in cells was the objective of this presentation. Several themes of actuality were addressed including genotoxicity of light, the primary prevention of skin cancers, the field actinodermatosis and cancerogenesis, the skin cancer epidemiology, the duality of skin melanomas with contrasted prognoses, and the recognition of melanoma stem cells.

In the last years, several experimental biotherapies have been developed to treat Parkinson's disease. Initially, fetal dopaminergic transplants were proposed. Although a proof of concept and encouraging results have been provided, limitations of this treatment emerged over the years and the failure of controlled trials have conducted to a pause in the development of strategies based on fetal cells. Alternative approaches such as the use of retinal pigmented cells recently provided disappointing results in patients and much hope has now been reported on other sources of dopaminergic neurons such as those originating from stem cells. This strategy is however not yet ready for clinical trials in patients. Eventually, gene therapy is a new original experimental technique which has elicited several trials in the last few years some of them being promising.

Despite important progress in cardiology, acute myocardial infarction (AMI) is the major cause of congestive heart failure and subsequent mortality. The rationale for cell therapy to be administered after AMI is derived from the assumption that given the insufficient regeneration in the injured heart tissue, stem cells from the bone marrow may be able to replace or repair damaged vascular and cardiac tissue. Results of the first phase I clinical trials using bone marrow stem/progenitor cell therapy for AMI were published in 2002 to 2004. Although not designed to test the efficacy of the intervention, the initial trials indicated a promising improvement in a number of clinical outcomes and cardiac function and suggested the intervention was safe. Recently, randomized controlled trials of cardiac cell therapy for AMI were published, with mixed results. A meta-analysis including 13 trials with a total of 811 participants showed an improved left ventricular ejection fraction by 2.99%. A large multicentre international trial is warranted to further document the efficacy of cardiac cell therapy on clinical outcomes.

A cord blood graft is now frequently used in the context of allogeneic hematopoietic transplantation. In 2007, 27% of unrelated allotransplantations performed in France used a cord blood graft. In comparison to other sources of hematopoietic grafts, cord blood has a number of advantages (immediate availability of the graft, possibility of a lesser HLA compatibility between donor and recipient...) and inconveniences (a limited number of stem cells, increased risk of infectious complications...). Recently, the possibility of combining two cord blood grafts has been demonstrated. In 2007, 55% of unrelated cord blood grafts transplantation were performed as such. Results of multicentric studies published as of now, as well as considerable potential associated with cord blood transplantation requires important efforts to increase both the quantity and quality of cord blood grafts made available for transplantation.

Mast cell disorders are defined by the accumulation of mast cells in one or more organ systems. Cutaneous forms are mainly observed in children whereas systemic forms are predominant in adults. Mast cells cause symptoms by the release of proinflammatory mediators or by infiltration of various organs. The measurement of serum tryptase has opened the possibility of screening for mastocytosis, which must be taken into consideration in case of severe anaphylactic reactions. Definite diagnosis is established based on a biopsy of skin or bone marrow. An activating mutation of stem cell factor receptor c-kit is often found. Treatment is based on control of the symptoms triggered by mast cell degranulation. Moreover, novel treatment options targeting mast cell proliferation become available for clinical use.

One has been trying for several years to find a substitute for red blood cells (RBC). The development of chemical or natural molecules to replace hemoglobin has nevertheless proved difficult and artificial blood is still unattainable. We have described a methodology permitting the massive ex vivo production of mature human RBC having all the characteristics of native adult RBC from hematopoietic stem cells (HSC) of diverse origins: blood, bone marrow or cord blood. This protocol allows both massive expansion of the HSC/progenitors and their complete differentiation to the stage of perfectly functional mature RBC. The levels of amplification obtained (10(5) to 2 x 10(5)) are compatible with an eventual transfusion application. We discuss here the state of the art of this new concept and evoke the obstacles to be overcome to pass from the laboratory model to clinical practice. This concept of "cultured RBC" opens up potentially considerable therapeutic perspectives in the field of blood transfusion.