title: Proof of principle for transfusion of in vitro-generated red blood cells.
abstract: In vitro RBC production from stem cells could represent an alternative to classic transfusion products. Until now the clinical feasibility of this concept has not been demonstrated. We addressed the question of the capacity of cultured RBCs (cRBCs) to survive in humans. By using a culture protocol permitting erythroid differentiation from peripheral CD34(+) HSC, we generated a homogeneous population of cRBC functional in terms of their deformability, enzyme content, capacity of their hemoglobin to fix/release oxygen, and expression of blood group antigens. We then demonstrated in the nonobese diabetes/severe combined immunodeficiency mouse that cRBC encountered in vivo the conditions necessary for their complete maturation. These data provided the rationale for injecting into one human a homogeneous sample of 10(10) cRBCs generated under good manufacturing practice conditions and labeled with (51)Cr. The level of these cells in the circulation 26 days after injection was between 41% and 63%, which compares favorably with the reported half-life of 28 ± 2 days for native RBCs. Their survival in vivo testifies globally to their quality and functionality. These data establish the proof of principle for transfusion of in vitro-generated RBCs and path the way toward new developments in transfusion medicine. This study is registered at http://www.clinicaltrials.gov as NCT0929266.
authors: UPMC Paris, UMR_S938 CDR Saint-Antoine, Prolifération et Différenciation des Cellules Souches, France.
authors: Marie-Catherine
authors: MC
authors: Giarratana
authors: Hélène
authors: H
authors: Rouard
authors: Agnès
authors: A
authors: Dumont
authors: Laurent
authors: L
authors: Kiger
authors: Innocent
authors: I
authors: Safeukui
authors: Pierre-Yves
authors: PY
authors: Le Pennec
authors: Sabine
authors: S
authors: François
authors: Germain
authors: G
authors: Trugnan
authors: Thierry
authors: T
authors: Peyrard
authors: Tiffany
authors: T
authors: Marie
authors: Séverine
authors: S
authors: Jolly
authors: Nicolas
authors: N
authors: Hebert
authors: Christelle
authors: C
authors: Mazurier
authors: Nathalie
authors: N
authors: Mario
authors: Laurence
authors: L
authors: Harmand
authors: Hélène
authors: H
authors: Lapillonne
authors: Jean-Yves
authors: JY
authors: Devaux
authors: Luc
authors: L
authors: Douay
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000097:blood; D001789:Blood Group Antigens / Q000097:blood; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004905:Erythrocyte Aging; D004907:Erythrocyte Deformability; D017707:Erythrocyte Transfusion / Q000379:methods*; D004912:Erythrocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004920:Erythropoiesis; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34; D001789:Blood Group Antigens; D006454:Hemoglobins