Importance of Microglia in Neurodegenerative Disease and Immunity

The body’s first line of defense against foreign substances is the immune system. This protects against disease and infection. The immune system consists of a complex network of cells and organs that work together to recognize and then destroy any harmful substances, keeping them contained at the source of the infection. Macrophages, which engulf and destroy anything dangerous via phagocytosis, play a critical role in this process.

Macrophages are derived from circulating peripheral blood monocytes. Monocytes move rapidly to tissue infection site during an immune response. Here they differentiate into specialized tissue macrophages. Monocytes responding to an infection in the liver, for example, differentiate into Kupffer cells, whereas in the alveoli of the lungs, they become alveolar macrophages.

Microglia are another of these tissue specific macrophages. In the central nervous system (CNS), they are one of the primary forms of immune defense. This article discusses the origins of microglia and their role in the immune response. It also explains why microglia are of increasing interest to researchers studying neurodegenerative disease and development of drugs.

Where do Microglia Come from and What do They do?

Incredible progress has been made over the past few years with regards to understanding the functions and origins of microglia. It is now understood that they originate from yolk-sac macrophage progenitors that migrate to the CNS during early embryogenesis, and as such are present from birth.

Under inflammatory conditions in adults, circulating monocytes are recruited to the CNS. Here, they differentiate into microglia. According to recent research, both the proliferation and differentiation of macrophages depend on the presence of a set of transcription factors and growth factor receptors (which include colony-stimulating factor 1 (CSF1) and PU.1 receptors) in the tissue where the monocytes settle.

Microglia are critical to many important functions in the CNS, including the maintenance of neural networks and regulation of brain development. In addition, they have a significant role in the immune response. Here, they mediate neuroinflammation to repair neuronal injury as well as removing any antigens that could endanger the CNS.

Why are Microglia Important Cells to Study in Disease Research?

Microglia have a critical role in the inflammatory response to CNS disease and injury and as such can become activated and/or dysregulated in neurodegenerative disease processes like Parkinson’s and Alzheimer’s diseases. The pro-inflammatory activation of microglia, for example, can induce the death of dopaminergic neurons and so contribute to the progression of Parkinson’s disease. Therefore, great interest has been generated surrounding microglia as indicators of neurodegenerative disease and also around their potential as therapeutic targets.

The conventional method for studying microglia was, until recently, in vivo animal models (for example, chemical or genetic disease mimicking in mice). However,  due to their limited physiological relevance and therefore translation to humans, these models have come under scrutiny. Animal models also limit the study of multicellular interactions between the microglia and neighboring cells, like astrocytes and neurons, and this is important in neurodegenerative disease pathologies.

Axol iPSC-Derived Macrophages show expression of the ionized calcium-binding adapter molecule 1 (IBA1), which is typically expressed by macrophages/microglia upon activation.

Axol iPSC-Derived Macrophages show expression of the ionized calcium-binding adapter molecule 1 (IBA1), which is typically expressed by macrophages/microglia upon activation.

Recent advances in stem cell biology have provided an alternative approach. It is now possible to generate macrophages from human induced pluripotent stem cells (hiPSCs) for use in in vitro experiments.

How can hiPSC-Derived Macrophages Benefit Research?

Axol produces a broad range of hiPSC-Derived cells that can be used in disease research and drug discovery. This includes the generation of hiPSC-Derived Monocytes and Macrophages. These cells can be co-cultured alongside the CNS tissue of choice, producing specialized microglial cells. Moreover, they can be co-cultured in three-dimensional culture systems with neurons and other glial cells to mimic in vivo multicellular interactions. This provides a model of neurodegenerative disease that has even greater physiological relevance.

Compared to traditional sources of macrophages and monocytes from peripheral blood and immortalized cell lines (e.g. THP-1), hiPSC-Derived Macrophages from Axol have various advantages. One such advantage is that, unlike commercially available myeloid cell lines that show an abnormal karyotype and proliferate in vitro, hiPSC-Derived Macrophages from Axol do not proliferate because they are terminally differentiated.

Furthermore, blood samples produce a mixed culture of cells and so a lower proportion of macrophages. This means that donor samples need to be pooled and this can reduce the reproducibility of experiments. Since hiPSC-Derived Macrophages from Axol are generated from hiPSC-Derived Monocytes and are produced from one stable donor, they produce much purer macrophage populations that do not need to be pooled.

About AXOL Biosciences

Axol specializes in human cell culture.

Axol produces high quality human cell products and critical reagents such as media and growth supplements. We have a passion for great science, delivering epic support and innovating future products to help our customers advance faster in their research.

Our expertise includes reprogramming cells to iPSCs and then differentiating to various cell types. We supply differentiated cells derived from healthy donors and patients of specific disease backgrounds. As a service, we also take cells provided by customers (primary or iPSC) and then do the reprogramming (when necessary) and differentiation. Clearly, by offloading the burden of generating cells, your time is freed up to focus on the research. Axol holds the necessary licenses that are required to do iPSC work.

The package wouldn't be complete without optimized media, coating solutions and other reagents. Our in-house R&D team works hard to improve on existing media and reagents as well as innovate new products for human cell culture. We also supply a growing range of human primary cells; making Axol your first port of call for your human cell culture needs.


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Last updated: Oct 15, 2019 at 4:16 AM

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