Novel organoid model enables study of microglia in health and disease

Scientists develop a new human brain organoid to include immune cells, making it more realistic for physiological and pathological research.

In a landmark paper published in Cell (PMID: 37172564), a team lead by Professor Gage at the Salk Institute, La Jolla California, demonstrate a novel model called the immunocompetent human brain organoid (iHBO) that allows the study of human pluripotent stem cell-derived microglia within vascularized human brain organoids. This model successfully replicates the developmental program and immune-sensing state of microglia, demonstrates the influence of the human brain environment on microglial gene expression, and enables the examination of microglial phenotypes in response to physiological and pathological conditions.

Figure: Graphical abstract by Schafer et al. Cell (PMID: 37172564).

In this paper, Schafer et al. developed cortical organoids derived from human pluripotent stem cells and observed a key feature microglial entry into the developing human brain which is the efficient invasion of erythromyeloid progenitors (EMPs) within the organoids. This colonization was found to be most effective between days 35 and 42 of development. The EMP-derived microglia-like cells assumed primitive, ramified-like morphologies after six weeks in vitro, indicating the environment was insufficient for the cells to acquire the characteristics of mature microglia. To overcome this limitation, the authors transplanted these organoids into mice with no native microglia, which was successful, and enabled the EMP-derived microglia to survive long-term and develop into mature, homeostatic microglia that closely resembled those found in the human brain.

In conclusion, the development of this novel organoid model is of huge importance to the neuroscience community as it provides the opportunity to investigate the interaction between microglia and the human neuronal environment during development and disease.

The authors used the following HumanKine® recombinant proteins for their organoid development:

About Proteintech’s HumanKine Proteins

HumanKine recombinant proteins are created in HEK293 cells using animal free components. Proteins co-expressed in bacteria will not possess post- translational modifications, e.g., phosphorylation or glycosylation. For activity, many proteins require glycosylation and processing available exclusively in eukaryotic systems; specifically human systems for authentic human proteins.

All Humankine® recombinant proteins are produced in Proteintech's in-house cGMP grade laboratory adhering to strict quality control regulationsd disease.

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