A new laboratory protocol could make it far easier to generate one of the immune system’s most versatile cell types. Scientists led by Nico Lachmann, PhD, at Hannover Medical School have developed a standardized method to produce macrophages from induced pluripotent stem cells (iPSCs) using an intermediate-scale benchtop bioreactor.

Macrophages are central players in immunity, tissue repair, and disease progression, making them valuable tools in regenerative medicine, cancer research, and drug discovery. Yet producing these cells in a controlled, reproducible way—especially at volumes suitable for early-stage research—has remained a challenge. Many academic labs still rely on small, two-dimensional culture systems that are labor-intensive and prone to variability.

The new protocol addresses this gap by enabling macrophage production in suspension cultures within a compact bioreactor designed for volumes between 10 and 50 mL. The approach extends earlier large-scale manufacturing methods but adapts them for smaller, more accessible systems suited to academic research and preclinical studies.

The workflow unfolds over roughly 24 days and proceeds through two major milestones. First, iPSCs are coaxed into forming mesoderm-primed aggregates with hematopoietic potential—structures known as “hemanoids.” These aggregates then undergo hematopoietic differentiation, yielding mature macrophages that are ready for downstream applications without additional maturation steps.

Using this system, researchers can collect macrophages repeatedly over long-term cultures. Each vessel produces tens of millions of cells per harvest, and multiple collections can be obtained from a single culture. The bioreactor simultaneously monitors key environmental parameters—including temperature, pH, and carbon dioxide levels—and it improves reproducibility and cell quality compared with traditional open-culture methods.

Lachmann and his colleagues designed this system with usability in mind. The semi-automated platform requires minimal hands-on time and does not demand advanced bioprocessing expertise, making it accessible to laboratories with basic stem cell culture experience.

Beyond simplifying cell production, the method could expand experimental possibilities. iPSC-derived macrophages can be integrated into organoids, organ-on-chip systems, and disease models to better replicate human physiology in vitro. Such models are increasingly used to study inflammatory diseases, neurodegeneration, cardiovascular disorders, and cancer.

The standardized cell supply could also support emerging drug-safety assays and immunotherapy development. As researchers seek alternatives to animal testing and more human-relevant systems, scalable immune cell—manufacturing platforms may become an essential part of the experimental toolkit and commercial bioprocessing.

By bridging the gap between small-scale culture plates and industrial bioreactors, the new protocol provides a practical middle ground—one that could accelerate macrophage-based research across many fields and contribute to advances in biopharmaceutical manufacturing.

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