A5010896897- Pluripotent Stem Cells Research
- Liver physiology and pathology
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- Lipoproteins and Cardiovascular Health
- Tissue Engineering and Regenerative Medicine
- Renal and related cancers
- 3D Printing in Biomedical Research
- Neuroscience and Neural Engineering
- Biomedical Ethics and Regulation
- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- RNA Research and Splicing
- Genomics and Rare Diseases
- Erythrocyte Function and Pathophysiology
- Cardiac electrophysiology and arrhythmias
- Lipid metabolism and disorders
- Cancer Mechanisms and Therapy
- Endoplasmic Reticulum Stress and Disease
- Cardiac Ischemia and Reperfusion
- Anesthesia and Neurotoxicity Research
- Hemoglobinopathies and Related Disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
- PI3K/AKT/mTOR signaling in cancer
- Skin and Cellular Biology Research
Institut du Thorax
2015-2025
Centre National de la Recherche Scientifique
2013-2025
Inserm
2013-2025
Nantes Université
2013-2025
Centre Hospitalier Universitaire d'Angers
2021
Matrix Research (United States)
2014
Université Paris-Sud
2012-2013
Université Paris-Saclay
2013
Charité - Universitätsmedizin Berlin
2013
Bicêtre Hospital
2012-2013
There exists a worldwide shortage of donor livers available for orthotropic liver transplantation and hepatocyte therapies. In addition to their therapeutic potential, primary human hepatocytes facilitate the study molecular genetic aspects hepatic disease development provide platform drug toxicity screens identification novel pharmaceuticals with potential treat wide array metabolic diseases. The demand hepatocytes, therefore, heavily outweighs availability. As an alternative using as...
Abstract Background The use of lentiviruses to reprogram human somatic cells into induced pluripotent stem (iPS) could limit their therapeutic usefulness due the integration viral DNA sequences genome recipient cell. Recent work has demonstrated that iPS can be generated using episomal plasmids, excisable transposons, adeno or sendai viruses, mRNA, recombinant proteins. While these approaches offer an advance, protocols have some drawbacks. Commonly procedures require either subcloning...
The availability of pluripotent stem cells offers the possibility using such to model hepatic disease and development. With this in mind, we previously established a protocol that facilitates differentiation both human embryonic induced into share many characteristics with hepatocytes. use highly defined culture conditions avoidance feeder or embryoid bodies allowed synchronous reproducible occur. towards hepatocyte-like fate appeared recapitulate developmental stages normally associated...
Abstract Background To maintain pluripotency of human embryonic stem (huES) cells in feeder-free culture it has been necessary to provide a Matrigel substratum, which is complex poorly defined extracellular matrices and growth factors derived from mouse Engelbreth-Holm-Swarm sarcoma cells. Culture under ill-defined conditions can inhibit the effectiveness maintaining pluripotent state reduce reproducibility differentiation protocols. Moreover recent batches have found be contaminated with...
Elevated levels of low-density lipoprotein cholesterol (LDL-C) in plasma are a major contributor to cardiovascular disease, which is the leading cause death worldwide. Genome-wide association studies (GWAS) have identified 95 loci that associate with control lipid/cholesterol metabolism. Although GWAS results highly provocative, direct analyses contribution specific allelic variations regulating LDL-C has been challenging due difficulty accessing appropriate cells from affected patients. The...
Secondary erythrocytosis often results from conditions that cause tissue hypoxia or an improper increase in erythropoietin (EPO) production. EPO, the major regulator of erythropoiesis, has a complex and tightly regulated expression during development, with liver-to-kidney switch shortly after birth. We identified six families was associated circulating EPO levels within normal range characterized as novel molecular functional entity. investigated effect pathogenic variants using...
Loss of the nuclear hormone receptor hepatocyte factor 4α (HNF4α) in hepatocytes results a complex pleiotropic phenotype that includes block differentiation and severe disruption to liver function. Recent analyses have shown hepatic gene expression is severely affected by absence HNF4α, with 567 genes reduced ≥2.5-fold (P ≤ 0.05) Hnf4α−/− fetal livers. Although many these are direct targets, HNF4α has also been regulate other transcription factors, this raises possibility dependence on for...
Background Human genetically inherited cardiac diseases have been studied mainly in heterologous systems or animal models, independent of patients' genetic backgrounds. Because sources human cardiomyocytes ( CM s) are extremely limited, the use urine samples to generate induced pluripotent stem cell–derived s would be a noninvasive method identify dysfunctions that lead pathologies within specific The objective was validate CMs differentiated from urine‐derived (UhiPS) cells as new cellular...
ABSTRACT Proprotein convertase subtilisin kexin type 9 (PCSK9) is a critical modulator of cholesterol homeostasis. Whereas PCSK9 gain-of-function (GOF) mutations are associated with autosomal dominant hypercholesterolemia (ADH) and premature atherosclerosis, loss-of-function (LOF) have cardio-protective effect in some cases can lead to familial hypobetalipoproteinemia (FHBL). However, limitations the currently available cellular models preclude deciphering consequences mutation further. We...
Abstract Over a decade after their discovery, induced pluripotent stem cells (iPSCs) have become major biological model. The iPSC technology allows generation of from somatic bearing any genomic background. challenge ahead us is to translate human iPSCs (hiPSCs) protocols into clinical treatment. To do so, we need improve the quality hiPSCs produced. In this study report reprogramming multiple patient urine-derived cell lines with mRNA reprogramming, which, date, one fastest and most...
Abstract Intra‐hepatic invasion is a key feature of hepatocellular carcinoma (HCC) progression. We have shown that human liver myofibroblasts induce HCC cells through Matrigel, via the secretion hepatocyte growth factor (HGF). In our study, we investigated role matrix metalloproteinases (MMP) in HGF‐induced invasion. Marimastat, synthetic MMP inhibitor, dose‐dependently decreased HepG2 with maximum 82.7 ± 13.3% at 20 μM. TIMP‐2, natural up to 51.2 11.2% 200 ng/ml. To determine target for...
Human embryonic stem cell (hESC)-derived cardiomyocytes potentially represent a powerful experimental model complementary to myocardium obtained from patients that is relatively inaccessible for research purposes. We tested whether anesthetic-induced preconditioning (APC) with isoflurane elicits competent protective mechanisms in hESC-derived against oxidative stress be used as of human studying preconditioning.H1 hESC line was differentiated into using growth factors activin A and bone...
We recently reported that, following induction of clumps pluripotent H1 human embryonic stem cells (hESCs) with activin-A and Bmp4 in defined medium for 5 days, widespread differentiation rhythmically contracting cardiomyocytes occurs within 3–4 weeks. In this study, the same approach was used to assess whether induced (hiPSCs), which may theoretically provide an unlimited source patient-matched transplantation therapy, can similarly undergo cardiomyocyte differentiation. Differentiation...
Abstract The liver plays a key role in the metabolism of lipoproteins, controlling both production and catabolism. To accelerate development new lipid‐lowering therapies humans, it is essential to have relevant vitro study model available. current hepatocyte‐like cells (HLCs) models derived from hiPSC can be used many genetically driven diseases but require further improvement better recapitulate complexity functions. Here, we aimed improve maturation HLCs using three‐dimensional (3D)...
Background: Atherosclerotic cardiovascular disease is the main cause of mortality worldwide and strongly influenced by circulating low-density lipoprotein (LDL) cholesterol levels. Only a few genes causally related to plasma LDL levels have been identified so far, only 1 gene, ANGPTL3 , has combined hypocholesterolemia. Here, our aim was elucidate genetic origin an unexplained hypocholesterolemia inherited in 4 generations French family. Methods: Using next-generation sequencing, we novel...
Hereditary erythrocytosis is a rare hematologic disorder characterized by an excess of red blood cell production. Here we describe European collaborative study involving collection 2,160 patients with sequenced in ten different laboratories. We focused our on the EGLN1 gene and identified 39 germline missense variants including one deletion 47 probands. encodes PHD2 prolyl 4-hydroxylase, major inhibitor hypoxia-inducible factor. performed comprehensive to evaluate causal role variants: (i)...
Abstract Background Human pluripotent stem cells (hPSCs) hold great promise for applications in regenerative medicine. However, the safety of cell therapy using differentiated hPSC derivatives must be improved through methods that will permit transplantation homogenous populations a specific type. To date, purification progenitors and mature generated from either embryonic or induced remains challenging with use conventional methods. Results We used lentivectors encoding green fluorescent...
Abstract Human induced pluripotent stem (hiPS) cell technology has already revolutionized some aspects of fundamental and applied research such as study disease mechanisms pharmacology screening. The first clinical trial using hiPS cell‐derived cells began in Japan, only 10 years after the publication proof‐of concept article. In this exciting context, strategies to generate have evolved quickly, tending towards non‐invasive protocols sample somatic combined with “safer” reprogramming...
This manuscript proposes an efficient and reproducible protocol for the generation of genetically modified human induced pluripotent stem cells (hiPSCs) by genome editing using CRISPR-Cas9 technology. Here, we describe experimental strategy generating knockout (KO) knockin (KI) clonal populations hiPSCs single-cell sorting flow cytometry. We efficiently achieved up to 15 kb deletions, molecular tag insertions, single-nucleotide in hiPSCs. emphasize efficacy this approach terms cell culture...