Ex-vivo generation of human red cells for transfusion

The present article reviews the recent data concerning the generation of red blood cells from haematopoietic stem cells using laboratory culture and discusses the potential for generating cultured red cells in sufficient quantity for use in transfusion practice.

Functional human reticulocytes have been generated from adult peripheral blood haematopoietic stem cells in laboratory culture without the use of heterologous feeder cells and their viability was demonstrated in vivo. Human erythroid progenitor cells lines have been produced from cord and human induced pluripotent stem cell (hiPSC) haematopoietic progenitors.

Availability of cultured human red cells from haematopoietic stem cells in the quantities required for transfusion therapy would have a major impact on healthcare provision worldwide. Recent studies provide cause for optimism that this ambitious goal is achievable. Functional adult reticulocytes have been made in culture and shown to survive in vivo. Erythroid progenitor cell lines have been derived from cord blood and from human induced pluripotent stem cells, suggesting that large-scale culture of erythroid cell lines and their differentiation to reticulocytes will be possible. Significant problems remain. More efficient enucleation and induction of maturation to an adult phenotype will be required in order to exploit high proliferative capacity of human embryonic stem cells and hiPSCs. Novel bioengineering solutions will be required to generate cultured red cells in the large quantities required, and in this context, use of synthetic three-dimensional scaffolds to mimic the bone marrow niche holds great promise for the future.