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[This corrects the article DOI: 10.3389/fbioe.2020.00620.].
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Cell therapy products exhibit great therapeutic potential but come with a deterring price tag partly caused by their costly manufacturing processes. The development of strategies that lead to cost-effective cell production is key to expand the reach of cell therapies. Growth factors are critical culture media components required for the maintenance and differentiation of cells in culture and are widely employed in cell therapy manufacturing. However, they are expensive, and their common use in soluble form is often associated with decreased stability and bioactivity. Immobilization has emerged as a possible strategy to optimize growth factor use in cell culture. To date, several immobilization techniques have been reported for attaching growth factors onto a variety of biomaterials, but these have been focused on tissue engineering. This review briefly summarizes the current landscape of cell therapy manufacturing, before describing the types of chemistry that can be used to immobilize growth factors for cell culture. Emphasis is placed to identify strategies that could reduce growth factor usage and enhance bioactivity. Finally, we describe a case study for stem cell factor.
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Neutropenia is a common side-effect of acute myeloid leukemia (AML) chemotherapy characterized by a critical drop in neutrophil blood concentration. Neutropenic patients are prone to infections, experience poorer clinical outcomes, and require expensive medical care. Although transfusions of donor neutrophils are a logical solution to neutropenia, this approach has not gained clinical traction, primarily due to challenges associated with obtaining sufficiently large numbers of neutrophils from donors whilst logistically managing their extremely short shelf-life. A protocol has been developed that produces clinical-scale quantities of neutrophils from hematopoietic stem and progenitor cells (HSPC) in 10 L single-use bioreactors (1). This strategy could be used to mass produce neutrophils and generate sufficient cell numbers to allow decisive clinical trials of neutrophil transfusion. We present a bioprocess model for neutrophil production at relevant clinical-scale. We evaluated two production scenarios, and the impact on cost of goods (COG) of multiple model parameters including cell yield, materials costs, and process duration. The most significant contributors to cost were consumables and raw materials, including the cost of procuring HSPC-containing umbilical cord blood. The model indicates that the most cost-efficient culture volume (batch size) is ~100 L in a single bioreactor. This study serves as a framework for decision-making and optimization strategies when contemplating the production of clinical quantities of cells for allogeneic therapy.