Jean Gekas

Myoblasts Derived From Normal hESCs and Dystrophic hiPSCs Efficiently Fuse With Existing Muscle Fibers Following Transplantation

Human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) have an endless self-renewal capacity and can theoretically differentiate into all types of lineages. They thus represent an unlimited source of cells for therapies of regenerative diseases, such as Duchenne muscular dystrophy (DMD), and for tissue repair in specific medical fields. However, at the moment, the low number of efficient specific lineage differentiation protocols compromises their use in regenerative medicine. We developed a two-step procedure to differentiate hESCs and dystrophic hiPSCs in myogenic cells. The first step was a culture in a myogenic medium and the second step an infection with an adenovirus expressing the myogenic master gene MyoD. Following infection, the cells expressed several myogenic markers and formed abundant multinucleated myotubes in vitro. When transplanted in the muscle of Rag/mdx mice, these cells participated in muscle regeneration by fusing very well with existing muscle fibers. Our findings provide an effective method that will permit to use hESCs or hiPSCs for preclinical studies in muscle repair.

Comparison of different strategies in prenatal screening for Down's syndrome: cost effectiveness analysis of computer simulation.

Objectives To assess and compare the cost effectiveness of three different strategies for prenatal screening for Down’s syndrome (integrated test, sequential screening, and contingent screenings) and to determine the most useful cut-off values for risk. Design Computer simulations to study integrated, sequential, and contingent screening strategies with various cut-offs leading to 19 potential screening algorithms. Data sources The computer simulation was populated with data from the Serum Urine and Ultrasound Screening Study (SURUSS), real unit costs for healthcare interventions, and a population of 110 948 pregnancies from the province of Québec for the year 2001. Main outcome measures Cost effectiveness ratios, incremental cost effectiveness ratios, and screening options’ outcomes. Results The contingent screening strategy dominated all other screening options: it had the best cost effectiveness ratio (

Amniotic stem cells for cellular cardiomyoplasty: promises and premises.

C26 833 per case of Down’s syndrome) with fewer procedure related euploid miscarriages and unnecessary terminations (respectively, 6 and 16 per 100 000 pregnancies). It also outperformed serum screening at the second trimester. In terms of the incremental cost effectiveness ratio, contingent screening was still dominant: compared with screening based on maternal age alone, the savings were

Rapid testing versus karyotyping in Down's syndrome screening: cost-effectiveness and detection of clinically significant chromosome abnormalities

C30 963 per additional birth with Down’s syndrome averted. Contingent screening was the only screening strategy that offered early reassurance to the majority of women (77.81%) in first trimester and minimised costs by limiting retesting during the second trimester (21.05%). For the contingent and sequential screening strategies, the choice of cut-off value for risk in the first trimester test significantly affected the cost effectiveness ratios (respectively, from

In vitro and in vivo study of human amniotic fluid-derived stem cell differentiation into myogenic lineage.

C26 833 to

Cost-effectiveness and accuracy of prenatal Down syndrome screening strategies: should the combined test continue to be widely used?

C37 260 and from

Current perspectives on the etiology of agnathia-otocephaly

C35 215 to

Cost effectiveness of newborn screening for cystic fibrosis: A simulation study

C45 314 per case of Down’s syndrome), the number of procedure related euploid miscarriages (from 6 to 46 and from 6 to 45 per 100 000 pregnancies), and the number of unnecessary terminations (from 16 to 26 and from 16 to 25 per 100 000 pregnancies). Conclusions Contingent screening, with a first trimester cut-off value for high risk of 1 in 9, is the preferred option for prenatal screening of women for pregnancies affected by Down’s syndrome.

PRENATAL DIAGNOSIS AND MOLECULAR GENETIC STUDIES ON A NEW CASE OF AGNATHIA-OTOCEPHALY

Cellular cardiomyoplasty is undergoing intensive investigation as a new form of therapy for severely damaged hearts. Among several cell types, mesenchymal stem cells (MSCs) have been proposed as a potential cell source. MSC can be found in adult tissues or in fetal tissues like the umbilical chord blood, amniotic membrane, or amniotic fluid (AF). AF‐MSCs have properties intermediate between embryonic and adult MSC, which make them particularly attractive for cellular regeneration. It has been shown that MSC could differentiate in cardiomyocytes‐like cells in vitro. In some animal models, it has also been shown that transplanted MSC could engraft and show some cardiomyocytes‐like characteristics. Since MSC do not express HLA‐DR and present in vitro and in vivo immunosuppressive properties, they can be envisioned to be used in allogenic cellular cardiomyoplasty. Based on these promises, MSC from adult donors are currently used in small safety and feasibility trials. No clinical trial using AF‐MSC has been performed yet. Still, the exact role of true cell repopulation and in situ cardiomyocytes differentiation versus pure paracrine effect after cell transplantation is currently much debated. Cellular cardiomyoplasty is a fascinating new area of investigation in regenerative medicine. Although considerable knowledge has been gained over the last decade on the use of MSC as a potential stem cell (SC) source, many issues remain unsolved. Because of several limitations in animal models, clinical studies in highly selected patients balancing the risks and benefits are required. In that regard, MSCs obtained from the fetal AF are a potential new source of SCs that need to be further investigated for cellular cardiomyoplasty.

Identification of trisomy 18, trisomy 13, and Down syndrome from maternal plasma

In all, 80% of antenatal karyotypes are generated by Downs syndrome screening programmes (DSSP). After a positive screening, women are offered prenatal foetus karyotyping, the gold standard. Reliable molecular methods for rapid aneuploidy diagnosis (RAD: fluorescence in situ hybridization (FISH) and quantitative fluorescence PCR (QF-PCR)) can detect common aneuploidies, and are faster and less expensive than karyotyping.In the UK, RAD is recommended as a standalone approach in DSSP, whereas the US guidelines recommend that RAD be followed up by karyotyping. A cost-effectiveness (CE) analysis of RAD in various DSSP is lacking. There is a debate over the significance of chromosome abnormalities (CA) detected with karyotyping but not using RAD. Our objectives were to compare the CE of RAD versus karyotyping, to evaluate the clinically significant missed CA and to determine the impact of detecting the missed CA. We performed computer simulations to compare six screening options followed by FISH, PCR or karyotyping using a population of 110 948 pregnancies. Among the safer screening strategies, the most cost-effective strategy was contingent screening with QF-PCR (CE ratio of