Enhanced Ex Vivo Generation of Erythroid Cells from Human Induced Pluripotent Stem Cells in a Simplified Cell Culture System with Low Cytokine Support

Bernecker, Claudia; Ackermann, Mania; Lachmann, Nico; Rohrhofer, Lisa; Zaehres, Holm; Araúzo‐Bravo, Marcos J.; Akker, Emile van den; Schlenke, Peter; Dorn, Isabel

doi:10.1089/scd.2019.0132

Cited by 48 publications

(64 citation statements)

References 50 publications

(87 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HSCs can be mobilized from the bone marrow into the peripheral blood using hematopoietic colony-stimulating factors, allowing the convenient harvest of these cells for clinical transplantation [ 64 ]. The ex vivo proliferation and differentiation of developing erythrocytes demands on external signals, such as EPO, SCF, and IL-3, allowing for the regular production of mature and transfusable units of RBCs [ 65 , 66 ]. It is now possible to enrich for erythroid progenitors and precursors to a much greater extent than has been possible before with impact on application to regenerative medicine [ 67 , 68 ].…”

Section: Ex Vivo Generation Of Developing Erythrocytesmentioning

confidence: 99%

Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome

Detzner

Pohlentz

Müthing

2020

Toxins

View full text Add to dashboard Cite

The global emergence of clinical diseases caused by enterohemorrhagic Escherichia coli (EHEC) is an issue of great concern. EHEC release Shiga toxins (Stxs) as their key virulence factors, and investigations on the cell-damaging mechanisms toward target cells are inevitable for the development of novel mitigation strategies. Stx-mediated hemolytic uremic syndrome (HUS), characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal injury, is the most severe outcome of an EHEC infection. Hemolytic anemia during HUS is defined as the loss of erythrocytes by mechanical disruption when passing through narrowed microvessels. The formation of thrombi in the microvasculature is considered an indirect effect of Stx-mediated injury mainly of the renal microvascular endothelial cells, resulting in obstructions of vessels. In this review, we summarize and discuss recent data providing evidence that HUS-associated hemolytic anemia may arise not only from intravascular rupture of erythrocytes, but also from the extravascular impairment of erythropoiesis, the development of red blood cells in the bone marrow, via direct Stx-mediated damage of maturing erythrocytes, leading to “non-hemolytic” anemia.

show abstract

Section: Ex Vivo Generation Of Developing Erythrocytesmentioning

confidence: 99%

Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome

Detzner

Pohlentz

Müthing

2020

Toxins

View full text Add to dashboard Cite

show abstract

“…The expansion rate of SiBBE during differentiation is in line with that of our immortalised normal erythroid cell lines (BEL-A 19 and additional lines; paper in preparation). iPSC lines created from β-thalassemia patient cells have the potential to provide a sustainable source of cells, with the reported expansion potential of differentiated erythroid cells from normal iPSC higher than SiBBE but varying widely (33 to 800 fold [25][26][27] ). However, the cells exhibit aberrant or incomplete erythroid differentiation and express predominantly foetal/embryonic rather than adult globin 12,14,15 making them unsuitable for model lines.…”

Section: Increased Foetal Globin On Treatment Of Sibbe With Hydroxyureamentioning

confidence: 99%

Generation of an immortalised erythroid cell line from haematopoietic stem cells of a haemoglobin E/β-thalassemia patient

Trakarnsanga

Tipgomut

Metheetrairut

et al. 2020

Sci Rep

View full text Add to dashboard Cite

The β-thalassemia syndromes are the most prevalent genetic disorder globally, characterised by reduced or absent β-globin chain synthesis. HbE/β-thalassemia is a subtype of β-thalassemia with extremely high frequency in Asia. Studying molecular defects behind β-thalassemia is severely impeded by paucity of material from patients and lack of suitable cell lines. Approaches to derive erythroid cells from induced pluripotent stem cells (iPSCs) created from patients are confounded by poor levels of erythroid cell expansion, aberrant or incomplete erythroid differentiation and foetal/embryonic rather than adult globin expression. In this study we generate an immortalised erythroid cell line from peripheral blood stem cells of a HbE/β-thalassemia patient. Morphological analysis shows the cells are proerythroblasts with some early basophilic erythroblasts, with no change in morphology over time in culture. The line differentiates along the erythroid pathway to orthochromatic erythroblasts and reticulocytes. Importantly, unlike iPSCs, the line maintains the haemoglobin profile of the patient’s red blood cells. This is the first human cellular model for β-thalassemia providing a sustainable source of disease cells for studying underlying disease mechanisms and for use as drug screening platform, particularly for reagents designed to increase foetal haemoglobin expression as we have additionally demonstrated with hydroxyurea.

show abstract

“…Among these is stratification of patients concerning the response to therapies, taking into account all the phenotypic/genotypic characteristics, and designing optimal treatments (e.g., for stimulation of HbF, iron chelation) targeting various symptoms at the individual patient's level (personalized medicine). Finally, the Biobank might provide a cell template for gene manipulation of HSC or iPSC for each patient [60].…”

Section: Bio-banking Of Erythroid Cellsmentioning

confidence: 99%

Erythropoiesis In Vitro—A Research and Therapeutic Tool in Thalassemia

Fibach

2019

JCM

View full text Add to dashboard Cite

Thalassemia (thal) is a hereditary chronic hemolytic anemia due to a partial or complete deficiency in the production of globin chains, in most cases, α or β, which compose, together with the iron-containing porphyrins (hemes), the hemoglobin molecules in red blood cells (RBC). The major clinical symptom of β-thal is severe chronic anemia—a decrease in RBC number and their hemoglobin content. In spite of the improvement in therapy, thal still severely affects the quality of life of the patients and their families and imposes a substantial financial burden on the community. These considerations position β-thal, among other hemoglobinopathies, as a major health and social problem that deserves increased efforts in research and its clinical application. These efforts are based on clinical studies, experiments in animal models and the use of erythroid cells grown in culture. The latter include immortal cell lines and cultures initiated by erythroid progenitor and stem cells derived from the blood and RBC producing (erythropoietic) sites of normal and thal donors, embryonic stem cells, and recently, "induced pluripotent stem cells" generated by manipulation of differentiated somatic cells. The present review summarizes the use of erythroid cultures, their technological aspects and their contribution to the research and its clinical application in thal. The former includes deciphering of the normal and pathological biology of the erythroid cell development, and the latter—their role in developing innovative therapeutics—drugs and methods of gene therapy, as well as providing an alternative source of RBC that may complement or substitute blood transfusions.

show abstract

Enhanced Ex Vivo Generation of Erythroid Cells from Human Induced Pluripotent Stem Cells in a Simplified Cell Culture System with Low Cytokine Support

Cited by 48 publications

References 50 publications

Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome

Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome

Generation of an immortalised erythroid cell line from haematopoietic stem cells of a haemoglobin E/β-thalassemia patient

Erythropoiesis In Vitro—A Research and Therapeutic Tool in Thalassemia

Contact Info

Product

Resources

About