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Microglia Differentiation Service

Overview Our Service Published Data Applications FAQs Scientific Resources Related Services

By providing high-quality and customized solutions, Creative Biolabs is a reliable partner for your neuroscience research. Our specialized scientist team provides tailored STEMOD™ ex vivo model services for microglia differentiation to meet every specific demand of our customers.

Introduction to Microglia

Microglia are the macrophage population of the central nervous system (CNS), belonging to the glial system that supports and protects neuronal functions. Microglia are broadly distributed in the brain and the spinal cord and represent the most important first immune defense of the CNS. They are phagocytic, cytotoxic, antigen-presenting cells that promote brain tissue repair after injury. More recently, a growing number of studies demonstrate the large number of functions covered by these cells that are now considered to play a major role in development, homeostasis, and various neurologic and psychiatric diseases.

  • Differentiation of Microglia
  • They arise from primitive myeloid progenitors in the yolk sac that differentiate to microglial progenitors and invade the developing brain. Once in the nervous parenchyma, microglial cells increase in number and disperse throughout the CNS; these cells finally differentiate into fully ramified microglial cells. In the brain with an intact blood-brain barrier (BBB), microglia persist as a self-sustained population.

  • Functions of Microglia
  • Microglia has two main functional aspects, including immune defense and CNS maintenance. Microglia functions lead to a sudden spike in reactive oxygen species (ROS) levels generated by the stimulation of the NADPH oxidase. This mechanism is a characteristic feature of microglia to protect the brain from pathogens. Microglia maintain the brain homeostasis and reside in the healthy CNS in a resting but surveillant state and promote homeostasis through reciprocal signaling interactions with neurons. Moreover, some emerging data shows that microglia have new and fundamental roles in controlling neuronal proliferation and differentiation and in the formation of synaptic connections.

Brain development and microglial homeostasis. Fig.1 Brain development and microglial homeostasis. (Ginhoux, 2013)

  • Microglia Markers
  • Microglia can express the Csf-1 receptor (Csf-1R), the fractalkine receptor (Cx3cr1), and the integrin CD11b for their development. Another essential transcription factor for microglia development is PU.1, which regulates Csf-1R, among other genes. In addition, the calcium-binding protein Iba-1 is often used as a marker of microglia. The identification of microglia-specific markers is valuable for distinguishing the myeloid cells during neuroinflammatory diseases and to assess their contributions to brain homeostasis.

  • Diseases Related to Microglia
  • Microglia is crucial to the proper development and maintenance of the CNS and is involved in numerous neurological disorders. Chronic activation of microglia is a trigger to the progression of multiple sclerosis and Parkinson's disease, and defective phagocytosis and synaptic pruning have been implicated in schizophrenia and autism spectrum disorders. Microglia also contribute to the progression of diseases such as multiple sclerosis, Parkinson's disease, HIV dementia, amyotrophic lateral sclerosis, Huntington's disease, Pick's disease, brain tumors, and prion disease. Therefore, microglia occupy a central position in the defense and maintenance of the CNS and attract interest as therapeutic targets in neurological disorders and recovery from brain injury. The therapeutic use of microglia has been demonstrated in experimental animal models of human diseases.

Strategy for directed differentiation of microglial precursors from pluripotent stem cells.

Microglia Differentiation Service

Microglia is present as important for CNS function. However, difficulties in procuring human microglia have limited their study and hampered the clinical translation of microglia-based treatments shown to be effective in animal disease models. In recent years, pluripotent stem cells can be already widely used in directed differentiation into astrocytes and microglia and neuronal subtypes of the CNS, opening new possibilities for disease modeling and developing patient-specific therapies. Active in the market of neuroscience ex vivo models, Creative Biolabs is considered a leading provider of the class of astrocyte differentiation services worldwide. Our STEMOD™ ex vivo models can offer reproducible and scalable differentiation protocols to create deeper functional studies to meet all specific requirements.

With many years of experience, Creative Biolabs provides a wide range of STEMOD™ neuroscience ex vivo model services. Our dedicated staff and advanced equipment enable us to identify processes of astrocyte differentiation that are the most suitable for your development. For more information, please click here.

Our service process, based on stem cell technologies, utilizes iPSCs as a fundamental resource, which are treated with a cocktail of factors to direct their differentiation into microglial cells. The process of differentiation is carefully monitored to ensure the generation of pure, functional microglia.

  • Our service is fully customizable. Cell maturity, quantity, genetic background, and potential genetic modifications can be adjusted to meet the specific requirements of your research pathway.
  • Our team of experts strictly adheres to quality assurance and quality control norms to ensure the delivery of standardized and high-quality services.
  • We strive to streamline the cell acquisition procedure so that researchers can focus on their experiments, advancing the ongoing research in neuroscience.

We are committed to providing timely, reliable, and high-quality services to serve and advance the forefront of biotechnology research. We also offer flexibility in our services, including but not limited to:

Services Descriptions
Custom Brain Organoid Services Based on our advanced platform, Creative Biolabs now provides custom brain organoid services, including forebrain organoids, cerebellar organoids, whole-brain organoids, as well as retinal organoids.
Blood-Brain Barrier Model Our service begins with creating a custom, personalized BBB model using client-specified factors. This can be from a variety of cell types, including induced pluripotent stem cells (iPSCs), primary cells, or immortalized cell lines. These personalized models mimic the human BBB's tight-junctional complex, in a superior manner, provide a more accurate prediction of a drug's BBB permeability.
STEMOD™ Advanced Drug Discovery Service We have developed a comprehensive technology platform to provide one-stop CNS drug discovery services. Our platform has advanced neuroscience ex vivo models, neuroscience assay techniques, and neuroscience research tools. These technologies will cover every important stage of CNS drug discovery, resulting in a one-stop shop for our customers.

Published Data

SW Chen et al. reported a novel approach that produces, within 10 days, the differentiation of human induced pluripotent stem cells (hiPSCs) into microglia (iMG) by forced expression of both SPI1 and CEBPA. They confirmed the high level of expression and cellular purity of major microglia markers by RT-qPCR, immunostaining and flow cytometry analysis. These iMGs exhibited appropriate physiological functions, including various inflammatory responses, ADP/ATP-induced migration and phagocytosis.

As shown, RT-qPCR was performed to detect the mRNA expression levels of key microglia markers, including TMEM119, C1QA, GPR34, CD11b and stem cell markers, such as POU5F1. Cell immunostaining for microglia markers IBA1, TREM2, CD11b, TMEM119, P2RY12, PU.1/SPI1 and DAPI was performed. CD11b+ or TREM2+ cells in iMG were quantified by flow cytometry. Differentiation efficiency was shown as the ratio of the total number of IBA1+ to DAPI+ cells.

Characterization of hiPSC-derived microglia-like cells.(Chen, Shih-Wei, et al., 2021)Fig. 2 Characterization of hiPSC-derived microglia-like cells.2

Applications

Through our custom service, we assist clients in transforming iPSCs or ESCs into functional microglia cells. This enables researchers to develop microglia-specific disease models, perform drug screening, elucidate cellular behaviors, and uncover the underpinnings of numerous neurological conditions.

  • Customizable Cell Differentiation: Depending on the unique requirements of your research, we can methodically manipulate multiple variables - from growth conditions and culture matrices to differentiation protocols.
  • Drug Discovery and Toxicity Testing: Microglia cells derived through our service can be used for potency, efficacy, and toxicity testing of candidates in drug pipeline development.
  • Disease Modeling and Basic Research: Generate in-depth in vitro disease models and delineate the role of microglia in neuroinflammation, neurodegeneration, and CNS disorders.
  • Cellular Therapies: Enable the development of groundbreaking microglia-based cellular therapies for a range of neurodegenerative and CNS diseases.
  • Biomarker Discovery: By employing the derived microglial cells, researchers can discover novel biomarkers of various brain-related diseases.

FAQs

Q: Can you provide microglia samples that mimic specific disease states?

A: Yes. By leveraging advanced cell culture techniques and our aim to meet your unique research needs, we can provide microglia samples that mimic different disease states. This is beneficial for studying the pathophysiology of disorders like Alzheimer's, Parkinson's, or other neurodegenerative conditions.

Q: Do you offer support or consultation in the experimental design phase?

A: Yes, we do offer consultation services. Our expert team is available to guide you through the experimental design phase, offering advice on microglia preparation, storage, and usage in your specific research paradigm, as we understand that these factors significantly impact experimental outcomes.

Q: What different parameters can be customized for microglia samples?

A: Microglia samples can be customized based on various parameters, such as cell density, co-culture conditions, and specific activation states. This way, we can deliver a product that adheres closely to your research objectives and experimental design, thereby fostering a more accurate and streamlined research process.

Q: What kind of quality assurance do you provide?

A: We ensure that all our differentiated microglia cells undergo a rigid quality control process involving scientific validation for microglia identity, purity, and functionality. Our qualified team validates each batch using thorough genomic, proteomic, and functional characterizations. We are committed to supplying high-quality and reliable microglia cellular products to meet your research needs.

Q: What happens if the sample delivered does not meet my expectations or requirements?

A: Our main aim is to ensure complete customer satisfaction, so if there are any concerns over the delivered sample, we request that customers contact us immediately. Our qualified team will work closely with you to address any issues and find an appropriate solution.

Scientific Resources

References

  1. Tremblay, M. È.; et al. The role of microglia in the healthy brain. Journal of Neuroscience. 2011, 31(45), 16064-16069.
  2. Chen, Shih-Wei, et al. "Efficient conversion of human induced pluripotent stem cells into microglia by defined transcription factors." Stem Cell Reports 16.5 (2021): 1363-1380.

For Research Use Only. Not For Clinical Use.