A5050373396- Hemoglobinopathies and Related Disorders
- Erythrocyte Function and Pathophysiology
- Blood groups and transfusion
- Prenatal Screening and Diagnostics
- Iron Metabolism and Disorders
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Hemoglobin structure and function
- Hematopoietic Stem Cell Transplantation
- Parvovirus B19 Infection Studies
- Cardiac electrophysiology and arrhythmias
- Bone and Joint Diseases
- Hematological disorders and diagnostics
- Cytokine Signaling Pathways and Interactions
- Renal Transplantation Outcomes and Treatments
- RNA modifications and cancer
- Analytical Methods in Pharmaceuticals
- Computational Drug Discovery Methods
- Renal and related cancers
- Cancer Genomics and Diagnostics
- Chemical and Physical Properties in Aqueous Solutions
- Virus-based gene therapy research
- Blood disorders and treatments
- Carcinogens and Genotoxicity Assessment
- Neonatal Health and Biochemistry
Établissement Français du Sang
2015-2025
Université Paris-Est Créteil
2018-2025
Institut Mondor de Recherche Biomédicale
2017-2025
Université de Rouen Normandie
2025
Inserm
2011-2024
Hôpitaux Universitaires Henri-Mondor
2020-2023
Société de Réanimation de Langue Française
2023
Assistance Publique – Hôpitaux de Paris
2020-2022
Fondation Maladies Rares
2021
Centre de Recherche Saint-Antoine
2011-2016
Background Ex vivo manufacture of red blood cells from stem is a potential means to ensure an adequate and safe supply cell products. Advances in somatic reprogramming human induced pluripotent have opened the door generating specific for therapy. Human represent potentially unlimited source erythroid generation transfusion medicine.Design Methods We characterized differentiation maturation lines obtained fetal (IMR90) adult fibroblasts (FD-136) compared those embryonic line (H1). Our...
Background Human induced pluripotent stem cells offer perspectives for cell therapy and research models diseases. We applied this approach to the normal pathological erythroid differentiation model by establishing from homozygous sickle disease donors.Design Methods addressed question as whether these can reach complete terminal maturation notably with a switch fetal adult hemoglobin. Sickle were differentiated in vitro into red blood characterized their terms of hemoglobin content, oxygen...
Flexible electrode systems capable of monitoring in vivo changes venous and myocardial extracellular potassium activity were constructed using valinomycin-polyvinyl chloride matrix membrane polyvinyl tubing. Electrode impedance was 1--30 Momega, time constant 10--200 ms, drift less than 1 mV/h, shelf life approximately 3 days (intramyocardial electrode) 6 wk (venous electrode). In vitro accuracy determined 5 dogs 18 pigs, anesthetized with sodium pentobarbital (35 mg/kg iv), normal elevated...
Abstract In sickle cell disease (SCD), the β6 Glu→Val substitution in β-globin leads to red blood sickling. The transplantation of autologous, genetically modified hematopoietic stem and progenitor cells (HSPCs) is a promising treatment option for patients with SCD. We completed Phase I/II open-label clinical trial (NCT03964792) SCD using lentiviral vector (DREPAGLOBE) expressing potent anti-sickling β-globin. primary endpoint was evaluate short-term safety secondary endpoints included...
While enucleation is a critical step in the terminal differentiation of human red blood cells, molecular mechanisms underlying this unique process remain unclear. To investigate erythroblast enucleation, we studied erythroid embryonic stem cells (hESCs), which provide model for deeper understanding development and multiple cell types. First, using two-step protocol, demonstrated that from hESCs directly dependent on age embryoid bodies. Second, by choosing two extreme conditions culture,...
Abstract We previously reported initial clinical results of post-transcriptional gene silencing BCL11A expression (NCT 03282656) reversing the fetal to adult hemoglobin switch. A goal this approach is increase (HbF) while coordinately reducing sickle (HbS) expression. The resulting combinatorial effect should prove effective in inhibiting HbS polymerization at lower physiologic oxygen values thereby mitigating disease complications. Here we report exploratory single-cell analysis patients...
Polymerization of the sickle hemoglobin (HbS) is a key determinant cell disease (SCD), an inherited blood disorder. Fetal (HbF) major modulator severity by both decreasing HbS intracellular concentration and inhibiting its polymerization. However, heterocellular distribution HbF common in SCD. For polymerization inhibition, hypothesis "HbF per red (HbF/RBC) threshold" requires accurate measurement individual RBC. To date, detection methods are limited to qualitative RBC populations...
Lentiviral modification combined with ex vivo erythroid differentiation was used to stably inhibit RhAG expression, a critical component of the Rh(rhesus) membrane complex defective in Rh(null) syndrome. The cultured red cells generated recapitulate major alterations native regarding antigen deformability, and gas transport function, providing proof principle for their use as model syndrome investigate Rh biogenesis human primary cells. Using this model, we were able reveal first time that...
The induction of micronucleated reticulocytes in the bone marrow is a sensitive indicator chromosomal damage. Therefore, micronucleus assay rodents widely used genotoxicity and carcinogenicity testing. A test system based on cultured human primary cells could potentially provide better prediction compared to animal tests, increasing patient safety while also implementing 3Rs principle, i.e. replace, reduce refine. Hereby, we describe development an vitro animal-free ex vivo culture red blood...
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All authors declare no conflict of interests. The data that support the findings this study are available on request from corresponding author. not publicly due to privacy or ethical restrictions.