High-Yield Monocyte, Macrophage, and Dendritic Cell Differentiation from Induced Pluripotent Stem Cells

Armitage, L. H.; Khosravi Maharlooei, M.; Meacham, A. M.; Butfiloski, E. J.; Viola, R. M.; Egli, D.; Sykes, M.; Wallet, M. A.; Mathews, C. E.

doi:10.1101/2021.04.29.441947

bioRxiv · 10.1101/2021.04.29.441947

High-Yield Monocyte, Macrophage, and Dendritic Cell Differentiation from Induced Pluripotent Stem Cells

Armitage, L. H.·Khosravi Maharlooei, M.·Meacham, A. M.·Butfiloski, E. J.·Viola, R. M.·Egli, D.·Sykes, M.·Wallet, M. A.·Mathews, C. E.

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Abstract

Differentiation of induced pluripotent stem cells (iPSC) into monocytes, monocyte-derived macrophages (MDM), and monocyte-derived dendritic cells (moDC) represents a powerful tool for studying human innate immunology and developing novel iPSC-derived immune therapies. Challenges include inefficiencies in iPSC-derived cell cultures, labor-intensive culture conditions, low purity of desired cell types, and feeder cell requirements. Here, a highly efficient method for differentiating monocytes, MDMs, and moDCs that overcomes these challenges is described. The process utilizes commercially-available materials to derive CD34+ progenitor cells that are apically released from a hemogenic endothelium. Subsequently, the hemogenic endothelium gives rise to highly pure (>95%), CD34-CD14+ monocytes in 19-23 days and yields 13.5-fold more monocytes by day 35 when compared to previous methods. These iPSC-monocytes are analogous to human blood-derived monocytes and readily differentiate into MDM and moDC. The efficient workflow and increase in monocyte output heightens feasibility for high throughput studies and enables clinical-scale iPSC-derived manufacturing processes.

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Armitage, L. H., Khosravi Maharlooei, M., Meacham, A. M., Butfiloski, E. J., Viola, R. M., Egli, D., Sykes, M., Wallet, M. A., Mathews, C. E.. 2021-04-29. High-Yield Monocyte, Macrophage, and Dendritic Cell Differentiation from Induced Pluripotent Stem Cells. https://doi.org/10.1101/2021.04.29.441947

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