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Engineering a Perfusion Bioreactor System for hiPSC-Derived Progenitor Co-Culture Capturing Microglial Features in

Catarina M Gomes1,2, Inês de Sá1,2, Margarida Delgado1,2

  • 1iBET, Instituto de Biologia Experimental e Biológica, Oeiras, Portugal.

Biotechnology and Bioengineering
|November 13, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed a scalable 3D co-culture model using human induced pluripotent stem cells (hiPSCs) to study microglia-neural cell interactions. This model effectively integrates hiPSC-derived erythromyeloid progenitors (iEMPs) with neurospheres, advancing central nervous system (CNS) research.

Keywords:
hiPSCsiEMPneurospheresstem cell bioengineeringstirred‐tank bioreactors

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Area of Science:

  • Neuroscience
  • Stem Cell Biology
  • Developmental Biology

Background:

  • Microglia are crucial for central nervous system (CNS) homeostasis and immune responses.
  • Existing human models struggle to replicate early and complex microglia-neural cell interactions.
  • Human induced pluripotent stem cells (hiPSCs) offer potential for modeling human development and disease.

Purpose of the Study:

  • To develop a scalable 3D co-culture system for studying microglia-neural cell interactions.
  • To differentiate hiPSC-derived erythromyeloid progenitors (iEMPs) and co-culture them with hiPSC-derived neurospheres.
  • To utilize the Ambr 250 Modular stirred-tank bioreactor (STB) system for a controlled and scalable environment.

Main Methods:

  • Differentiation of hiPSCs into iEMPs.
  • Formation of hiPSC-derived neurospheres.
  • 3D co-culture of iEMPs and neurospheres in an Ambr 250 Modular STB system.
  • Analysis of cell integration, morphology, transcription factor expression, and secretory profiles.

Main Results:

  • The STB system successfully supported iEMP integration into neurospheres, maintaining similar cell density and morphology.
  • The co-culture environment promoted microglial lineage commitment through upregulation of key transcription factors.
  • iEMP-neurospheres exhibited a distinct secretory profile, releasing factors vital for extracellular matrix remodeling and neuronal differentiation.

Conclusions:

  • hiPSC-derived iEMPs play a significant role in CNS development.
  • The developed 3D co-culture platform provides a robust and scalable model for preclinical research.
  • This model enhances the study of microglia-neural cell interactions in a controlled human-based system.