Blood Journal
Leading the way in experimental and clinical research in hematology

Proof of principle for transfusion of in vitro generated red blood cells

  1. Marie-Catherine Giarratana1,
  2. Hélène Rouard2,
  3. Agnès Dumont3,
  4. Laurent Kiger4,
  5. Innocent Safeukui5,
  6. Pierre-Yves Le Pennec6,
  7. Sabine François7,
  8. Germain Trugnan8,
  9. Thierry Peyrard6,
  10. Tiffany Marie9,
  11. Séverine Jolly10,
  12. Nicolas Hebert1,
  13. Christelle Mazurier1,
  14. Nathalie Mario11,
  15. Laurence Harmand1,
  16. Hélène Lapillonne12,
  17. Jean-Yves Devaux3, and
  18. Luc Douay1,*
  1. 1 UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Proliferation et Differentiation des Cellules Souches, Paris, France;
  2. 2 UPEC, Universite Paris Est Creteil, Creteil, France;
  3. 3 AP-HP Hopital St Antoine, Service de Medecine Nucleaire, Paris, France;
  4. 4 INSERM U473, Hopital du Kremlin-Bicetre, Kremlin-Bicetre, France;
  5. 5 CNRS URA 2581, Institut Pasteur, Molecular Immunology of Parasites Unit, Paris, France;
  6. 6 CNRGS, INTS, Paris, France;
  7. 7 IRSN, BP 17, Fontenay-aux-Roses, France;
  8. 8 UPMC Univ Paris 06; ERL INSERM U1057/UMR7203; FMPMC, Paris, France;
  9. 9 INSERM, UMR_S938, Proliferation et Differentiation des Cellules Souches, Paris, France;
  10. 10 EFS Ile de France, Unite d'Ingenierie et de Therapie Cellulaire, Creteil, France;
  11. 11 AP-HP, Hopital Saint-Antoine, Service de Biochimie A, Paris, France;
  12. 12 AP-HP, Hopital Trousseau, Service d'Hematologie Biologique, Paris, France
  1. * Corresponding author; email: luc.douay{at}sat.aphp.fr

Abstract

In vitro red blood cell (RBC) production from stem cells could represent an alternative to classical transfusion products. Up until now the clinical feasibility of this concept has not been demonstrated. We addressed the question of the capacity of cultured RBC (cRBC) to survive in human. 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 NOD/SCID 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 1010 cRBC generated under GMP conditions and labeled with 51Cr. The level of these cells in the circulation 26 days after injection lies between 41 and 63 % which compares favorably to the reported half-life of 28 ± 2 days for native RBC. Their survival in vivo testifies globally to their quality and functionality. These data establish the proof of principle for transfusion of in vitro generated RBC and path the way towards new developments in transfusion medicine. This study has been registered at clinicaltrials.gov as NCT0929266.

  • Submitted June 17, 2011.
  • Accepted July 7, 2011.