Lakhasly

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Red blood cell and platelet transfusions are routine life-saving procedures in medicine. While the relative ease of harvest and storage of these cell subsets enable this process, an adequate supply of suitable donor mate- rial remains problematic. The production of ex vivo- generated transfusible blood products, or Blood Pharm- ing, remains one of the most promising, as well as per- haps one of the most distant, deliverables of current cell expansion technologies. The current technical limita- tions are both biological and engineering in nature. We recently reviewed the individual challenges associated with production of red blood cells (RBCs), platelets, and neutrophils (25). The most promising culture methods for producing each cell product were reviewed and criti- cally analyzed for the feasibility of scaling these “best
practice” methods such that clinically relevant cell numbers could be generated. A key conclusion was that generating the necessary cell numbers, utilizing current best practice cell densities and expansion protocols, would require culture volumes that preclude the feasibil- ity of either RBC or platelet manufacture.
Our general inability to replicate the cell density and efficiency achieved within the human body is perhaps most strikingly appreciated by considering current meth- ods for RBC production. Utilizing the protocols devel- oped by Giarratana et al. (10), producing a single unit of RBCs (1012 cells) would require 660 L of medium (assuming a cell density of 3 × 106 cells/ml) or approxi- mately 9,500 traditional laboratory T175 flasks (25). In contrast to RBC manufacture, the ex vivo production of neutrophils for temporary immune support may be more feasible given the reduced necessary cell number (1010


Original text

Red blood cell and platelet transfusions are routine life-saving procedures in medicine. While the relative ease of harvest and storage of these cell subsets enable this process, an adequate supply of suitable donor mate- rial remains problematic. The production of ex vivo- generated transfusible blood products, or Blood Pharm- ing, remains one of the most promising, as well as per- haps one of the most distant, deliverables of current cell expansion technologies. The current technical limita- tions are both biological and engineering in nature. We recently reviewed the individual challenges associated with production of red blood cells (RBCs), platelets, and neutrophils (25). The most promising culture methods for producing each cell product were reviewed and criti- cally analyzed for the feasibility of scaling these “best
practice” methods such that clinically relevant cell numbers could be generated. A key conclusion was that generating the necessary cell numbers, utilizing current best practice cell densities and expansion protocols, would require culture volumes that preclude the feasibil- ity of either RBC or platelet manufacture.
Our general inability to replicate the cell density and efficiency achieved within the human body is perhaps most strikingly appreciated by considering current meth- ods for RBC production. Utilizing the protocols devel- oped by Giarratana et al. (10), producing a single unit of RBCs (1012 cells) would require 660 L of medium (assuming a cell density of 3 × 106 cells/ml) or approxi- mately 9,500 traditional laboratory T175 flasks (25). In contrast to RBC manufacture, the ex vivo production of neutrophils for temporary immune support may be more feasible given the reduced necessary cell number (1010

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