Development of a method for mass production of functional neutrophils derived from human induced pluripotent stem cells

Abstract

Granulocyte transfusion therapy (GTX) is a treatment for severe infections in patients with neutropenia, but is not widely used because it requires repeated apheresis from healthy donors to harvest sufficient neutrophils. Induced pluripotent stem cell (iPSC)-derived neutrophils are considered a promising solution to this problem, and several groups have reported methods for differentiating iPSCs into neutrophils. However, the differentiation process takes more than 14 days, and an expansion culture method that yields sufficient neutrophils for effective GTX must be developed. We have recently established iPSC-derived granulocyte progenitor cell lines that can be expanded in vitro, which could serve as a starting point for supplying sufficient iPSC-derived neutrophils in 4 days when GTX treatment is required. However, before this manufacturing method is ready for clinical use, its efficacy and safety must be evaluated and the method must be improved to comply with quality control standards for regenerative medicine products.