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Effective and Rapid Generation of Functional Neutrophils From Induced Pluripotent Stem Cells Using ETV2-Modified mRNA

Effective and Rapid Generation of Functional Neutrophils From Induced Pluripotent Stem Cells Using ETV2-Modified mRNA

Vera S Brok-Volchanskaya, David A Bennin, Kran Suknuntha, Lucas C Klemm, Anna Huttenlocher, Igor Slukvin

Stem Cell Reports. 2019 Dec 10;13(6):1099-1110.

PMID: 31708474

Abstract:

Human induced pluripotent stem cells (hiPSCs) can serve as a versatile and scalable source of neutrophils for biomedical research and transfusion therapies. Here we describe a rapid efficient serum- and xenogen-free protocol for neutrophil generation, which is based on direct hematoendothelial programming of hiPSCs using ETV2-modified mRNA. Culture of ETV2-induced hematoendothelial progenitors in the presence of GM-CSF, FGF2, and UM171 led to continuous production of generous amounts of CD34+CD33+ myeloid progenitors which could be harvested every 8-10 days for up to 30 days of culture. Subsequently, myeloid progenitors were differentiated into neutrophils in the presence of G-CSF and the retinoic acid agonist Am580. Neutrophils obtained in these conditions displayed a typical somatic neutrophil morphology, produced reactive oxygen species, formed neutrophil extracellular traps and possessed phagocytic and chemotactic activities. Overall, this technology offers an opportunity to generate a significant number of neutrophils as soon as 14 days after initiation of differentiation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP102121608	AM580		102121-60-8	Price

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