Why Industrial Production of Red Blood Cells From Stem Cells is Essential for Tomorrow’s Blood Transfusion

Douay, Luc

doi:10.2217/rme-2018-0025

Cited by 18 publications

(20 citation statements)

References 15 publications

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“…Many reports have described modifications and improvements of this two-phase liquid culture protocol. These included the use of defined cytokine cocktails, serum-free medium [24,25] and feeder layers. For example, the use of mouse bone marrow stromal cells (MS-5) in the last phase of the culture protocol facilitated the final maturation, producing nearly 100% enucleated RBC.…”

Section: Erythroid Cultures Derived From Progenitor Cellsmentioning

confidence: 99%

Erythropoiesis In Vitro—A Research and Therapeutic Tool in Thalassemia

Fibach

2019

JCM

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Thalassemia (thal) is a hereditary chronic hemolytic anemia due to a partial or complete deficiency in the production of globin chains, in most cases, α or β, which compose, together with the iron-containing porphyrins (hemes), the hemoglobin molecules in red blood cells (RBC). The major clinical symptom of β-thal is severe chronic anemia—a decrease in RBC number and their hemoglobin content. In spite of the improvement in therapy, thal still severely affects the quality of life of the patients and their families and imposes a substantial financial burden on the community. These considerations position β-thal, among other hemoglobinopathies, as a major health and social problem that deserves increased efforts in research and its clinical application. These efforts are based on clinical studies, experiments in animal models and the use of erythroid cells grown in culture. The latter include immortal cell lines and cultures initiated by erythroid progenitor and stem cells derived from the blood and RBC producing (erythropoietic) sites of normal and thal donors, embryonic stem cells, and recently, "induced pluripotent stem cells" generated by manipulation of differentiated somatic cells. The present review summarizes the use of erythroid cultures, their technological aspects and their contribution to the research and its clinical application in thal. The former includes deciphering of the normal and pathological biology of the erythroid cell development, and the latter—their role in developing innovative therapeutics—drugs and methods of gene therapy, as well as providing an alternative source of RBC that may complement or substitute blood transfusions.

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Section: Erythroid Cultures Derived From Progenitor Cellsmentioning

confidence: 99%

Erythropoiesis In Vitro—A Research and Therapeutic Tool in Thalassemia

Fibach

2019

JCM

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“…For example, an anemic mouse is most appropriate to study the oxygen delivery of cultured RBCs, whereas a deeply immunodeficient mouse is better suited for studies that question the survival of transplanted cells [ 7 ]. Clearly, human trials are far more complicated, and to date, there is only one report of testing manufactured RBCs on a single human recipient [ [8] , [9] , [10] , [11] , [12] , [13] ].…”

Section: The Choice Of Starting Source Materials and The Contributingmentioning

confidence: 99%

“…The utilization of circulating HSCs from the PB is challenging, since it is easier and less labor intensive than BM. HSC can be collected either in a steady state condition or after G-CSF priming [ [10] , [11] , [12] ]. Researchers have developed an in-vitro RBCs production protocol from PB and proved the therapeutic potential of generated RBCs both in the preclinical and clinical settings [ 18 ].…”

Section: The Choice Of Starting Source Materials and The Contributingmentioning

confidence: 99%

“…The ability of hESCs to differentiate into haematopoietic cells and thus, to the erythroid cell line, was studied with protocols involving EB formations and a co-culture system [ [9] , [10] , [11] , [12] ]. The stromal cells used in most experiments were derived from non-human cell lines.…”

Section: The Choice Of Starting Source Materials and The Contributingmentioning

confidence: 99%

“…Use of low-cost media and reagents, replacement of culture media with small molecules, omission of the feeder cells and generation of erythropoietic cell lines, may result in a more cost-effective product. Safety issues, such as accidental transmission of harmful agents and immunogenic reactions, may be overcome if the protocols used for the production of ex vivo RBCs comply with Good Manufacturing Practice (GMP) [ 11 , 12 , 15 ].…”

Section: The Obstacles That Need To Be Overcomementioning

confidence: 99%

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Trends and targets of various types of stem cell derived transfusable RBC substitution therapy: Obstacles that need to be converted to opportunity

Lanza

Seghatchian

2020

Transfusion and Apheresis Science

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A shortage of blood during the pandemic outbreak of COVID-19 is a typical example in which the maintenance of a safe and adequate blood supply becomes difficult and highly demanding. So far, human RBCs have been produced in vitro using diverse sources: hematopoietic stem cells (SCs), embryonic SCs and induced pluripotent SCs. The existing, even safest core of conventional cellular bioproducts destined for transfusion have some shortcoming in respects to: donor –dependency variability in terms of hematological /immunological and process/ storage period issues. SCs–derived transfusable RBC bioproducts, as one blood group type for all, were highly complex to work out. Moreover, the strategies for their successful production are often dependent upon the right selection of starting source materials and the composition and the stability of the right expansion media and the strict compliance to GMP regulatory processes. In this mini-review we highlight some model studies, which 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. However, all cultured products do not have an unlimited life due to the critical metabolic pathways or the metabolites produced. New bioreactors are needed to remove these shortcomings and the development of a new mouse model is required. Modern clinical trials based on the employment of regenerative medicine approaches in combination with novel large-scale bioengineering tools, could overcome the current obstacles in artificial RBC substitution, possibly allowing an efficient RBC industrial production.

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