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Creative Biolabs

hiPSC-derived Microglia Culture and Isolation Service

Microglia are the resident immune cells of the central nervous system (CNS). They play crucial roles in immune surveillance, responding to injury and pathogens, synaptic pruning, and neuronal support and protection. Dysfunctional microglial responses have been implicated in many neurological and neurodegenerative diseases.

Microglia can be derived from induced pluripotent stem cells (iPSCs) through specific differentiation protocols. iPSCs are stem cells reprogrammed from somatic cells like skin or blood cells back into a pluripotent state. The iPSCs can then be directed to become microglial progenitor cells that mature into functional microglia-like cells. Creative Biolabs offers custom services to generate iPSC-derived microglia for research applications.

Fig. 1 Human iPSC-derived microglia. (Badanjak, 2021)

Advantages Applications Assays Related Diseases

Key Advantages of iPSC-derived Microglia Include

  • Renewable sources avoiding the use of fetal/animal primary cells
    hiPSC-derived microglia provide an ethically uncontroversial and renewable source, avoiding the use of fetal or animal primary microglia cultures.
  • Obtain homogeneous populations of microglia
    Differentiation from clonal hiPSC lines can produce pure cultures of defined microglia.
  • Generate patient-specific microglia to model diseases
    By reprogramming from patients, hiPSC lines can produce microglia carrying disease-relevant genetic backgrounds for disease modeling.
  • Study microglial biology, function, and responses
    hiPSC-microglia enable interrogating basic microglial properties like phagocytosis, migration, and cytokine release in a dish.
  • Screen compounds modulating microglial activation states
    High-throughput compound screens can identify new therapeutics that modulate the inflammatory/neuroprotective activation states of microglia.

Applications of hiPSC-derived Microglia in Research

  • Modeling microglial involvement in neurological diseases
    Diseases like Alzheimer's, Parkinson's, and ALS can be modeled using patient microglia alongside hiPSC-derived neurons/astrocytes.
  • Investigating microglial-neuron interactions and signaling
    Co-culture systems allow studying how microglia influence neuronal development, function, and degeneration via secreted factors.
  • Developing microglia-based therapies and delivery vehicles
    Engineered hiPSC-microglia could act as vehicles for delivering neuroprotective factors or removing toxic protein aggregates.
  • Evaluating neuroinflammatory and neuroprotective pathways
    Genetic and compound perturbations enable delineating signaling cascades controlling pro- vs anti-inflammatory microglial phenotypes

Common Assays Utilize hiPSC-derived Microglia

  • Phagocytosis and oxidative stress functional assays

Assessing microglial phagocytic activity and production of reactive oxygen species which can damage neurons.

  • Co-cultures with hiPSC-derived neurons/astrocytes

Modeling interactions between microglia and other neural cell types by co-culturing in 2D/3D systems.

  • Inflammatory response/cytokine profiling assays

Quantifying secretion of pro-inflammatory cytokines like TNF-α, and IL-1β in response to immune challenges.

  • Compound screening for anti-inflammatory/neuroprotective effects

High-throughput screens to identify compounds that modulate microglial activation and improve neuronal survival.

  • RNA-sequencing and microglial signature analysis

Transcriptomic profiling to define gene expression patterns associated with different microglial activation states.

Microglial Dysfunction Has Been Linked To

  • Alzheimer's disease: Microglia implicated in amyloid-beta clearance

Microglia normally clear amyloid-beta plaques, but this function becomes impaired in Alzheimer's, exacerbating the disease.

  • Parkinson's disease: Neuroinflammation and oxidative stress

Overactive microglia induces oxidative stress and neuroinflammation that damages dopaminergic neurons in Parkinson's.

  • Multiple sclerosis: Microglial activation and CNS inflammation

In MS, aberrant microglial activation contributes to damaging CNS inflammation and demyelination of neurons.

  • Stroke: Microglia mediate post-ischemic neuroinflammation

After ischemic stroke injury, microglia become over-activated, causing oxidative damage and impairing neuronal recovery.

  • Autism spectrum disorders: Altered synaptic pruning

Microglia regulate synaptic pruning during development, and impairments may contribute to autism phenotypes.

hiPSC models allow studying patient microglia harboring disease-relevant genetic backgrounds. Researchers can investigate aberrant microglial responses, evaluate new therapeutics targeting microglia, and explore cell therapy approaches using hiPSC-derived microglia.

In summary, hiPSC-derived microglia serve as a powerful platform for studying microglial biology, and neuroinflammation and developing new therapies for various neurological conditions involving microglial dysfunction. Creative Biolabs provides hiPSC-derived microglia designed to meet the specific requirements of your project's research needs. Let us guide you through your experimental investigations and help advance your understanding of neuroinflammation.

Reference

  1. Badanjak, Katja et al. "iPSC-Derived Microglia as a Model to Study Inflammation in Idiopathic Parkinson's Disease." Front Cell Dev Biol. 2021;9:740758. Distributed under Open Access license CC BY 4.0. The original image was modified.
For Research Use Only. Not For Clinical Use.
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