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Article
Nature Biotechnology  23, 69 - 74 (2004)
Published online: 26 December 2004; | doi:10.1038/nbt1047

Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells

Marie-Catherine Giarratana1, Ladan Kobari1, Hélène Lapillonne1, 2, David Chalmers1, 3, Laurent Kiger4, Thérèse Cynober5, Michael C Marden4, Henri Wajcman6 & Luc Douay1, 2

1  Laboratoire d'Hématologie EA1638, Université Paris VI, CHU Saint Antoine, 27 rue de Chaligny-75571 Paris Cedex 12, France.

2  Service d'Hématologie Biologique, Hôpital Armand Trousseau, Assistance Publique Hôpitaux de Paris, 26 avenue du Dr Netter-75571 Paris Cedex 12, France.

3  EFS Bourgogne Franche Comte, Boulevard Fleming BP 1937 Besançon 25290, France.

4  INSERM U473, 84 rue du Général Leclerc, 94276 Le Kremlin-Bicêtre Cedex, France.

5  Laboratoire d'Hématologie, Centre Hospitalier de Bicêtre, 84 rue du Général Leclerc, 94276 Le Kremlin-Bicêtre Cedex, France.

6  INSERM U468, Hôpital Henri Mondor, 94010 Créteil, France.

Correspondence should be addressed to Luc Douay luc.douay@trs.aphp.fr
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 times 106-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.

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Nature Biotechnology
ISSN: 1087-0156
EISSN: 1546-1696
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