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cytokine

Large-scale production of red blood cells from stem cells: What are the technical challenges ahead?. cytokine. A biological odyssey. Main advances in RBC culture in view of the large-scale production of clinical grade cells. On the way to clinical applications. Three economic questions arise.

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cytokine

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

  2. cytokine

  3. A biological odyssey Main advances in RBC culture in view of the large-scale production of clinical grade cells

  4. On the way to clinical applications Three economic questions arise (i) Are there any fundamental barriers to large-scale manufacture of RBC? (ii) Is it possible to generate clinicallyrelevant numbers of cells?

  5. The price ①5 × 107 cells/mL, it would take 40 liters of culture media with a total cost of $8330 to generate enough cells (without considering the investment in facilities) Timmins, N. E., Nielsen, L. K., Blood cell manufacture: current methodsand future challenges. Trends Biotechnol. 2009, 27, 415–422. ②Zeuner et al. proposed a production price$8000–15 000 per unit of blood. Zeuner, A., Martelli, F., Vaglio, S., Federici, G. et al., Concise review:stem cell-derived erythrocytes as upcoming players in blood transfusion.Stem Cells 2012, 30, 1587–1596. $700–1200 hospital cost

  6. biotechnological breakthrough expansion and dilution CD34+ RBC seven 175-cm2 flasks 2 tennis courts

  7. medium price

  8. control of the pH pH glucose and glutamine metabolisms lactate ammonia metabolic byproducts pH decrease modification of osmolarity direct growth inhibitor cell metabolismslows down with higher cell density

  9. DO level Dissolved oxygen

  10. How to improve the culture conditions • It will be necessary to monitorat the same time the differentiation of the cells, whichwill imply a compromise betweenexpansion and maturation. • For RBC production,the complete medium is too expensive, withgrowth factors and other proteins representing morethan 90% of the price. Thus, a new method toeliminate waste products while conserving the expensivemolecules is needed. • All the downstream processwill have to be revised, with critical improvements toimplement in the separation and purification procedures.

  11. RBC production in bioreactors

  12. Day 21 expanded cell populations comprised a pure population oferythroid cells of mixed maturity 21 Day EBs at different stages of maturation

  13. Ultra-high-yield manufacture of RBC per UCB donation (5 × 106 CD34+ cells/donation) 108 107 500 units of RBC per UCB donation CD235 CD71

  14. hollow-fiber bioreactor

  15. Bioreactor perfusionschematic

  16. Bioreactor parameters

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