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

Marie-Catherine Giarratana, Hélène Rouard, Agnès Dumont, Laurent Kiger, Innocent Safeukui, Pierre-Yves Le Pennec, Sabine François, Germain Trugnan, Thierry Peyrard, Tiffany Marie, Séverine Jolly, Nicolas Hebert, Christelle Mazurier, Nathalie Mario, Laurence Harmand, Hélène Lapillonne, Jean-Yves Devaux, Luc Douay

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.