Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells.
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.
Giarratana
Marie-Catherine
MC
Laboratoire d'Hématologie EA1638, Université Paris VI, CHU Saint Antoine, 27 rue de Chaligny-75571 Paris Cedex 12, France.
Kobari
Ladan
L
Lapillonne
Hélène
H
Chalmers
David
D
Kiger
Laurent
L
Cynober
Thérèse
T
Marden
Michael C
MC
Wajcman
Henri
H
Douay
Luc
L
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology*; D015672:Erythroid Precursor Cells / Q000378:metabolism; D005434:Flow Cytometry; D015316:Genetic Therapy; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018613:Microscopy, Confocal; D010100:Oxygen / Q000378:metabolism; D012156:Reticulocytes / Q000166:cytology; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D014466:Ultraviolet Rays
D018952:Antigens, CD34; D016207:Cytokines; D006454:Hemoglobins; D010100:Oxygen