Abstract

Macrophages perform key
functions in regulating homeostasis, immune response and tissue repair.
Equally, their dysfunction may drive pathogenesis in inflammatory and
degenerative diseases, making them a key therapeutic target.

Currently, primary human macrophages are
differentiated from peripheral blood monocytes into monocyte-derived macrophages (MDMs), which is costly at scale and results in poor reproducibility due
to donor variability. Alternatively, immortalised cell systems such as THP-1
are used that lack human biological relevance.

Induced
pluripotent stem cells (iPSCs) generated from adult cells are self-renewing and can
potentially differentiate to any cell type derived from all three germ layers.
iPSC technology has provided new tools to improve drug discovery efforts from efficacy and toxicity testing to novel
target identification and understanding disease mechanisms.

Here we present
the establishment of a robust cellular
platform to generate a continuous supply of iPSC-derived macrophages (i-Mφ). The platform has been
validated in multiple iPSC donors. Several analyses to validate the i-Mφ against MDMs and THP-1
cells are presented, including cell surface marker expression, cytokine release
and RNA sequencing analysis. In addition an image analysis technique aiming to
predict i-Mφ production and quality is presented.