We describe here the large-scale ex vivo production of mature human red blood cells (RBCs) from hematopoietic stem cells of diverse origins. By mimicking the marrow microenvironment through the application of cytokines and coculture on stromal cells, we coupled substantial amplification of CD34(+) stem cells (up to 1.95 x 10(6)-fold) with 100% terminal differentiation into fully mature, functional RBCs. These cells survived in nonobese diabetic/severe combined immunodeficient mice, as do native RBCs. Our system for producing 'cultured RBCs' lends itself to a fundamental analysis of erythropoiesis and provides a simple in vitro model for studying important human viral or parasitic infections that target erythroid cells. Further development of large-scale production of cultured RBCs will have implications for gene therapy, blood transfusion and tropical medicine.
International Committee for Standardization in Haematology: recommended methods for red-cell enzyme analysis.
Characteristics of hexokinase, pyruvate kinase, and glucose-6-phosphate dehydrogenase during adult and neonatal reticulocyte maturation
Maintenance of the human malarial parasite, Plasmodium falciparum, in scid mice and transmission of gametocytes to mosquitoes
Erythropoietin-independent erythrocyte production: signals through gp130 and c-kit dramatically promote erythropoiesis from human CD34+ cells
Retrovirus packaging cells based on 10A1 murine leukemia virus for production of vectors that use multiple receptors for cell entry
Red cell abnormalities in hereditary spherocytosis: relevance to diagnosis and understanding of the variable expression of clinical severity
Murine endothelial cells support fetal liver erythropoiesis and myelopoiesis via distinct interactions
Clinical-scale human umbilical cord blood cell expansion in a novel automated perfusion culture system
Cell culture bags allow a large extent of ex vivo expansion of LTC-IC and functional mature cells which can subsequently be frozen: interest for a large-scale clinical applications
Direct contact between CD34+lin- cells and stroma induces a soluble activity that specifically increases primitive hematopoietic cell production
Presence of primitive lymphoid progenitors with NK or B potential in ex vivo expanded bone marrow cell cultures
In vitro and in vivo evidence for the long-term multilineage (myeloid, B, NK, and T) reconstitution capacity of ex vivo expanded human CD34(+) cord blood cells
Metabolic active-high density VERO cell cultures on microcarriers following apoptosis prevention by galactose/glutamine feeding
In vitro mass production of human erythroid cells from the blood of normal donors and of thalassemic patients
Flow cytometric characterization of perfused human bone marrow cultures: identification of the major cell lineages and correlation with the CFU-GM assay
Directed differentiation and mass cultivation of pure erythroid progenitors from mouse embryonic stem cells.
Growth of erythroid cells from thawed unseparated cord blood in vitro without exogenous erythropoietin
Human lymphohematopoietic reconstitution and immune function in immunodeficient mice receiving cotransplantation of human thymic tissue and CD34(+) cells.
Development of an enhanced B-specific lentiviral vector expressing BTK: a tool for gene therapy of XLA
The β-globin locus control region in combination with the EF1α short promoter allows enhanced lentiviral vector-mediated erythroid gene expression with conserved multilineage activity.
Extensive ex vivo expansion of functional human erythroid precursors established from umbilical cord blood cells by defined factors
Efficient enucleation of erythroblasts differentiated in vitro from hematopoietic stem and progenitor cells
Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice.
Ceramide glycosylation by glucosylceramide synthase selectively maintains the properties of breast cancer stem cells.
Enhanced production of red blood cells in suspension by electrostatic interactions with culture plates
Compartmental hollow fiber capillary membrane-based bioreactor technology for in vitro studies on red blood cell lineage direction of hematopoietic stem cells.
Block to the production of full-length B19 virus transcripts by internal polyadenylation is overcome by replication of the viral genome.
Ex vivo-generated CD36+ erythroid progenitors are highly permissive to human parvovirus B19 replication
Nuclear receptors TR2 and TR4 recruit multiple epigenetic transcriptional corepressors that associate specifically with the embryonic β-type globin promoters in differentiated adult erythroid cells.
Globin switches in yolk sac-like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells.
Tight control of MEK-ERK activation is essential in regulating proliferation, survival, and cytokine production of CD34+-derived neutrophil progenitors
Coupled transcription-splicing regulation of mutually exclusive splicing events at the 5' exons of protein 4.1R gene.
During EPO or anemia challenge, erythroid progenitor cells transit through a selectively expandable proerythroblast pool
Chromatin-modifying agents promote the ex vivo production of functional human erythroid progenitor cells
Maturing reticulocytes internalize plasma membrane in glycophorin A-containing vesicles that fuse with autophagosomes before exocytosis.
Immunohistochemical detection of phosphatidylserine and thrombospondin on denucleating erythroblasts in rat bone marrow
Biased, non-equivalent gene-proximal and -distal binding motifs of orphan nuclear receptor TR4 in primary human erythroid cells
Establishment of mouse embryonic stem cell-derived erythroid progenitor cell lines able to produce functional red blood cells.
Erythroid progenitor cells expanded from peripheral blood without mobilization or preselection: molecular characteristics and functional competence
Erythroid-specific expression of β-globin from Sleeping Beauty-transduced human hematopoietic progenitor cells.
CREs: Gene & Cell Therapy
Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.
Blood And Marrow Transplantation
The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.
Adult Stem Cells
Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.