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

@article{Rousseau2014LargescalePO,
  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},
  year={2014},
  volume={9}
}
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… Expand
Culturing red blood cells from stem cells: a solution to present and future challenges of transfusion medicine?
TLDR
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. Expand
The productivity limit of manufacturing blood cell therapy in scalable stirred bioreactors
TLDR
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. Expand
Trends and targets of various types of stem cell derived transfusable RBC substitution therapy: Obstacles that need to be converted to opportunity
TLDR
A mini-review of model studies showed that the efficiency and the functionality of RBCs that could be produced by the various types of SCs, in relation to the in-vitro culture procedures are such that they may, potentially, be used at an industrial level. Expand
Cell sources for large‐scale manufacture of red blood cells
TLDR
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. Expand
Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model
TLDR
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. Expand
Who Owns Hematopoietic Stem Cells? Some Fundamental Legal Stakes for the Manufacture of Cultured Red Blood Cells
TLDR
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. Expand
Purifying stem cell‐derived red blood cells: a high‐throughput label‐free downstream processing strategy based on microfluidic spiral inertial separation and membrane filtration
TLDR
A new route for high‐throughput purification process for in vitro manufactured red blood cells, leading to high mRBC purity while maintaining cell integrity and no alterations in their global gene expression profile is proposed. Expand
Superior survival of ex vivo cultured human reticulocytes following transfusion into mice
TLDR
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. Expand
Artificial Blood: A Futuristic Dimension of Modern Day Transfusion 
Sciences
TLDR
Artificial blood can complement the current blood products for transfusion and create a stable supply of safe and effective products to reduce the requirements of blood transfusions drastically especially in settings of trauma and surgery thereby reducing the reliance on banked donated blood. Expand
Plant cell-secreted stem cell factor stimulates expansion and differentiation of hematopoietic stem cells.
TLDR
This study exploited a proprietary technology, named HypGP engineering technology, for high-yield production of one of the key erythropoietic growth factors--stem cell factor (SCF)--in plant cell culture using a designer hydroxyproline-O-glycosylated peptide comprised of 20 tandem repeats of the "Ser-Pro" motif. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 119 REFERENCES
Concise Review: Stem Cell‐Derived Erythrocytes as Upcoming Players in Blood Transfusion
TLDR
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. Expand
Ultra-high-yield manufacture of red blood cells from hematopoietic stem cells.
TLDR
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. Expand
Banking of pluripotent adult stem cells as an unlimited source for red blood cell production: potential applications for alloimmunized patients and rare blood challenges.
TLDR
It is considered that a very limited number of RBC clones would be able to not only provide for the need for most alloimmunized patients and those with a rare blood group but also efficiently allow for a policy for alloIMmunization prevention in multiply transfused patients. Expand
Ex-vivo expansion of red blood cells: how real for transfusion in humans?
TLDR
Improvements in culture conditions and proof-of-principle studies in animal models have suggested that ex-vivo expanded red cells may represent such a product, and technical barriers to mass cell production will have been eliminated making transfusion with ex- vivo generated red cells a reality. Expand
Ex vivo production of human red blood cells from hematopoietic stem cells: what is the future in transfusion?
There is difficulty in obtaining adequate supplies of blood components, as well as disappointing performance of stabilized or recombinant hemoglobins, limited indications of oxygen transportersExpand
Red blood cells from induced pluripotent stem cells: hurdles and developments
TLDR
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. Expand
Blood cell manufacture: current methods and future challenges.
TLDR
Challenges in relation to current methods are discussed and how it might be possible to realize limited 'blood pharming' of neutrophils in the near future are discussed. Expand
Ex-vivo generation of human red cells for transfusion
TLDR
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. Expand
In vitro clinical‐grade generation of red blood cells from human umbilical cord blood CD34+ cells
TLDR
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. Expand
Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells
TLDR
The large-scale ex vivo production of mature human red blood cells from hematopoietic stem cells of diverse origins is described, which lends itself to a fundamental analysis of erythropoiesis and provides a simple in vitro model for studying important human viral or parasitic infections that target erythroid cells. Expand
...
1
2
3
4
5
...