Blood cell manufacture: current methods and future challenges

Timmins, Nicholas; Nielsen, Lars K.

doi:10.1016/j.tibtech.2009.03.008

Cited by 69 publications

(79 citation statements)

References 62 publications

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“…However, the complexity of a coculture system is a hindrance to the scaling-up of this process for industrial development. 16 Interestingly, replacement of the microenvironment by either FCS 17 or human serum in the presence 18 or absence of VEGF and IGF-II 19 permits the maturation of erythroid precursors into enucleated cells. Overall these data support the hypothesis of enucleation signals mediated by soluble factors probably secreted by the microenvironment.…”

Section: Introductionmentioning

confidence: 99%

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

Giarratana

Rouard

Dumont

et al. 2011

Blood

304

364

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In vitro RBC production from stem cells could represent an alternative to classic transfusion products. Until now the clinical feasibility of this concept has not been demonstrated. We addressed the question of the capacity of cultured RBCs (cRBCs) to survive in humans. By 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 nonobese diabetes/severe combined immunodeficiency 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 10 10 cRBCs generated under good manufacturing practice conditions and labeled with 51

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Section: Introductionmentioning

confidence: 99%

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

Giarratana

Rouard

Dumont

et al. 2011

Blood

304

364

View full text Add to dashboard Cite

show abstract

“…This is hypothesized that a cell density of 5×10 7 cells/ml should be produced regularly to support this much demand. It is estimated that production of single unit of blood through present static culture methods will require 660 liters of culturing medium and 9500 lab scale 175cm 2 culturing flasks (70ml medium/flask) [20][21][22]. This indicates the need for more automated 3D culture techniques to ensure such high production efficiency.…”

Section: The Fate Of Blood Production Is Regulated By Various Factorsmentioning

confidence: 99%

Blood Generation from Stem Cells: An Overview

Singh

Saini

Kumar

et al. 2016

IJSR

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“…Now that scientists are able to generate RBCs in vitro for transfusions, three economic questions arise: (i) how much money would we need to generate one blood unit, (ii) what would be the indications of this new product and (iii) what price would health insurance companies be able and willing to pay for it? To our knowledge, two teams have tried to extrapolate the cost of producing one blood unit [38,39]. On the basis of the realistic hypothesis that researchers will find the means of reaching a concentration of 5 × 10 7 cells/mL (ten times higher than today), Timmins et al [38] calculated that it would take 40 liters of culture media with a total cost of $8330 to generate enough cells.…”

Section: New Product New Pricementioning

confidence: 99%

“…To our knowledge, two teams have tried to extrapolate the cost of producing one blood unit [38,39]. On the basis of the realistic hypothesis that researchers will find the means of reaching a concentration of 5 × 10 7 cells/mL (ten times higher than today), Timmins et al [38] calculated that it would take 40 liters of culture media with a total cost of $8330 to generate enough cells. This takes into account the expenses for consumables, without considering the investment in facilities, but gives a good approximation of the cost of generating one blood unit.…”

Section: New Product New Pricementioning

confidence: 99%

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

Rousseau

Giarratana

Douay

2013

Biotechnology Journal

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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 switching from the current limited 2-dimensional production techniques to large-scale 3-dimensional bioreactors. In addition to requiring technological breakthroughs, the whole process also has to become at least five-fold more cost-efficient to match the current prices of high-quality blood products. The current review sums up the main biological advances of the past decade, outlines the key biotechnological challenges for the large-scale cost-effective production of red blood cells, proposes solutions based on strategies used in the bioindustry and presents the state-of-the-art of large-scale blood production.

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Blood cell manufacture: current methods and future challenges

Cited by 69 publications

References 62 publications

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

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

Blood Generation from Stem Cells: An Overview

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

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