Large‐scale production of red blood cells from stem cells: What are the technical challenges ahead?

  title={Large‐scale production of red blood cells from stem cells: What are the technical challenges ahead?},
  author={Guillaume F. Rousseau and M C Giarratana and Luc Douay},
  journal={Biotechnology Journal},
Blood‐transfusion centers regularly face the challenge of donor blood shortages, especially for rare blood groups. The possibility of producing universal red blood cells from stem cells industrially has become a possible alternative since the successful injection of blood generated in vitro into a human being in 2011. Although there remains many biological and regulatory issues concerning the efficacy and safety of this new product, the major challenge today for future clinical applications is… 

Culturing red blood cells from stem cells: a solution to present and future challenges of transfusion medicine?

The various obstacles that were overcome during the past decade to generate cRBC from various sources of stem cells (SC) and the next developments which will be required to achieve this goal are reported on.

The productivity limit of manufacturing blood cell therapy in scalable stirred bioreactors

The properties of erythroblasts are such that the conventional constraints on cell manufacturing efficiency, such as mass transfer and metabolic demand, should not prevent high intensity production; furthermore, this could be achieved in industry standard equipment.

Cell sources for large‐scale manufacture of red blood cells

Different approaches for the manufacture of erythrocytes, using more expandable precursor sources, are discussed, and the strategy of directly establishing immortalized erythroid progenitor cell lines is suitable forThe manufacture of RBCs.

Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model

The novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle) under resting and exercise-induced hypoxic conditions and provides support for further development as a transfusion product.

Who Owns Hematopoietic Stem Cells? Some Fundamental Legal Stakes for the Manufacture of Cultured Red Blood Cells

The various conceivable patterns of compensation for stem cell donors, from full-market compensation to full-free (i.e., uncompensated) donation, are examined and their respective relevance for the collection of suitable cell lines and for the development of the industry are discussed.

Superior survival of ex vivo cultured human reticulocytes following transfusion into mice

The study herein represents the first demonstration that ex vivo generated cultured red blood cells survive longer than donor red cells using an in vivo model that more closely mimics clinical transfusion.

Towards manufactured red blood cells for the treatment of inherited anemia

Recent progress in the erythroid culture field is discussed as well as opportunities for further scaling up of manufactured RBC production for transfusion practice.



Concise Review: Stem Cell‐Derived Erythrocytes as Upcoming Players in Blood Transfusion

Data on size, hemoglobin, and blood group antigen expression and phosphoproteomic profiling obtained on erythroid cells expanded ex vivo from a limited number of donors are presented as examples of the type of measurements that should be performed as part of the quality control to assess the suitability of these cells for transfusion.

Ultra-high-yield manufacture of red blood cells from hematopoietic stem cells.

A robust ultra-high-yield RBC expansion process is successfully developed capable of producing over 500 units of RBC per UCB donation using fully defined culture medium and it is shown that RBC can be efficiently produced in agitated bioreactor systems, demonstrating that no fundamental barriers exist to the manufacture of R BC using large-scale approaches.

Ex-vivo expansion of red blood cells: how real for transfusion in humans?

Ex vivo production of human red blood cells from hematopoietic stem cells: what is the future in transfusion?

Red blood cells from induced pluripotent stem cells: hurdles and developments

This review will focus on the recent findings about the generation of erythroid cells from induced pluripotent stem (iPS) cells and deals with the hurdles and next developments that will occur.

Blood cell manufacture: current methods and future challenges.

Ex-vivo generation of human red cells for transfusion

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.

In vitro clinical‐grade generation of red blood cells from human umbilical cord blood CD34+ cells

In vitro generation of clinically available RBCs from hematopoietic stem cells could be a promising new source to supplement the blood supply as there is no appropriate alternative source of red blood cells to relieve the worsening shortage of blood available for transfusion.

The hematopoietic stem cell niche: what are we trying to replicate?

This review briefly summarizes the current research efforts aimed at defining the appropriate in vivo conditions to be mimicked in ex vivo culture and proposes an approach to find the optimum conditions for this expansion utilizing smart surfaces and a criterion for developing these surfaces.