Construction, Characterization, and Neurological Disease Modeling of Microglia-Containing Brain Organoids
Construction, Characterization, and Neurological Disease Modeling of Microglia-Containing Brain Organoids
Microglia-containing human brain organoids (MC-HBOs) integrate neural cells, glial cells, and resident immune cells of the central nervous system within a three-dimensional culture system and can be used to analyze the roles of microglia in brain development, neuroinflammation, and neurodegenerative pathology. Compared with two-dimensional cultures and conventional brain organoids lacking immune components, this model is more suitable for investigating human neural-immune cell interactions, disease-associated phenotypes, and candidate-drug responses.
Keywords: microglia; brain organoids; MC-HBOs; induced pluripotent stem cells; neuroinflammation; Alzheimer’s disease; Parkinson’s disease; three-dimensional culture
1 Development and Functional Positioning of Microglia
1.1 Developmental Origin
Microglia are primarily derived from primitive myeloid progenitor cells in the embryonic yolk sac. These progenitor cells enter the developing brain during the early stages of central nervous system development and form a self-renewing microglial population after migration, colonization, and maturation. Their developmental origin and maintenance differ from those of most peripheral immune cells, which are continuously replenished by the bone marrow hematopoietic system.
Figure 1 Developmental origin, homeostatic maintenance, and aging-associated changes of microglia
1.2 Homeostatic Phenotype
Mature homeostatic microglia express markers including TMEM119, P2RY12, CX3CR1, and HEXB. Their transcriptional states and functional characteristics are continuously regulated by neurons, astrocytes, the extracellular matrix, and soluble factors. TGF-β-related signaling plays an important role in maintaining the homeostatic phenotype. When microglia are removed from the brain tissue environment or maintained under unsuitable culture conditions for extended periods, they may exhibit reduced P2RY12 and TMEM119 expression, increased inflammation-associated signaling, and altered phagocytic behavior.
1.3 Maintenance of Brain-Tissue Homeostasis
Microglia are widely distributed throughout the brain and spinal cord and continuously monitor the local microenvironment. They recognize cellular injury, abnormal protein deposition, and pathogen-associated signals and participate in the clearance of apoptotic cells and cellular debris. Their functions also include regulation of neurotransmitter and cytokine environments, support of neuronal survival, participation in synaptic pruning, and maintenance of neural-network structural stability.
1.4 Development and Synaptic Remodeling
During brain development, microglia participate in neural-circuit establishment by engulfing excess neural progenitors, clearing developmentally apoptotic cells, and selectively pruning synapses. Insufficient synaptic pruning may preserve abnormal connections, whereas excessive pruning may impair network integrity. Therefore, microglial research should not evaluate phagocytic capacity alone but should also assess synapse numbers, neuronal maturity, and electrophysiological activity to determine functional consequences.
1.5 Aging-Associated Changes
Aged microglia may exhibit reduced process complexity, enlarged cell bodies, decreased migratory capacity, increased lysosomal burden, and abnormal inflammatory regulation. Persistent protein aggregation, oxidative stress, and metabolic imbalance may further shift them from a homeostatic surveillance state toward a disease-associated reactive state, affecting abnormal protein clearance, synaptic protection, and inflammation resolution.
2 Microglial Dysfunction and Brain Diseases
2.1 Alzheimer’s Disease
In Alzheimer’s disease, microglia participate in Aβ recognition, uptake, and degradation and may form localized reactive structures around amyloid plaques. Their early responses may help restrict the spread of abnormal proteins, whereas persistent activation, insufficient lysosomal processing, or abnormal TREM2-associated signaling may reduce clearance efficiency and promote inflammatory-mediator release, complement activation, and synaptic loss.
2.2 Tau-Associated Pathology
Abnormally phosphorylated and aggregated Tau can be released from damaged neurons and affect neighboring cells. Microglia can internalize extracellular Tau, but insufficient degradation after uptake may cause persistent cellular stress and affect Tau propagation through neural tissue. Microglia-containing brain organoids can be used to distinguish direct Tau neurotoxicity from secondary inflammatory injury mediated by microglia.
2.3 Parkinson’s Disease
In Parkinson’s disease-related models, microglia can respond to α-synuclein aggregation, mitochondrial injury, and dopaminergic-neuron death. Persistent inflammatory signaling may aggravate oxidative stress and neuronal injury, whereas controlled phagocytosis and neurotrophic support may limit the accumulation of abnormal proteins and cellular debris.
2.4 Neuropsychiatric and Neuroimmune Diseases
Microglial abnormalities are also associated with schizophrenia, autism, bipolar disorder, multiple sclerosis, and other diseases. Microglial states in different diseases may involve abnormal synaptic pruning, insufficient clearance of myelin debris, enhanced antigen presentation, or persistent release of inflammatory factors and cannot be simply categorized as a single “pro-inflammatory” or “anti-inflammatory” phenotype.
3 Limitations of Conventional Research Models
3.1 Animal Models
Animal models retain integrated vascular, neural-circuit, and systemic immune environments and are suitable for studying disease progression and behavioral phenotypes. However, humans and experimental animals differ in brain-developmental timing, microglial transcriptional characteristics, immune responses, and disease-susceptibility genes, making it difficult to accurately reproduce certain human-specific pathological features and drug responses.
3.2 Two-Dimensional Microglial Culture
Two-dimensional culture facilitates variable control and high-throughput experiments but lacks three-dimensional tissue architecture, extracellular matrix, and complex cellular interactions. iPSC-derived microglia may rapidly change their morphology and transcriptional state in two-dimensional culture, with reduced expression of certain homeostatic markers, causing their responses to inflammatory stimuli and abnormal proteins to deviate from those observed in the brain.
3.3 Human Cell-Animal Chimeric Models
Transplantation of human microglial progenitor cells into animal brain tissue can provide a relatively complete tissue environment for cellular maturation but remains limited by host species, immune conditions, transplantation efficiency, and cross-species signal compatibility. This model is suitable for validating long-term engraftment and responses of cells in vivo but is difficult to apply to large-scale patient-specific screening.
3.4 Conventional Brain Organoids
Many directed neural-differentiation systems primarily generate neurons, neural progenitors, and certain astrocytes. Because microglia are derived from mesoderm-associated myeloid lineages, conventional neuroectodermal organoids generally lack microglia, limiting their application in research on neuroinflammation, immune clearance of abnormal proteins, and neural-immune interactions.
Table 1 Technical Characteristics of Different Microglial Research Models
Model | Major Advantages | Major Limitations | Suitable Research |
Two-dimensional microglial culture | Controllable conditions, simple operation, and suitability for high-throughput analysis | Homeostatic phenotype is readily lost, and three-dimensional cellular interactions are absent | Receptor signaling, preliminary drug screening, and phagocytosis assays |
Animal models | Preserve integrated neural, vascular, and immune environments | Species differences and limited reproduction of human pathology | Disease progression, behavioral studies, and systemic toxicology |
Human cell-animal chimeric models | Provide an in vivo maturation environment | Cross-species interactions, long experimental cycles, and low throughput | Human microglial engraftment and long-term function |
Conventional brain organoids | Simulate certain aspects of human brain development and three-dimensional structure | Generally lack microglia and vascular components | Neurodevelopment, genetic diseases, and neurotoxicity |
MC-HBOs | Preserve both three-dimensional neural architecture and human immune components | Complex batch variation, maturation control, and proportion control | Neuroinflammation, neurodegenerative diseases, and drug screening |
4 Construction Strategies for Microglia-Containing Brain Organoids
4.1 Preparation of Starting Cells
MC-HBOs generally use human induced pluripotent stem cells (hiPSCs) or human embryonic stem cells as starting materials. Cells should maintain stable pluripotency, a normal karyotype, and a low background level of spontaneous differentiation. Initial colony status, passage number, cell density, and recovery time after cryopreservation can all affect subsequent neural-organoid formation and myeloid-differentiation efficiency.
4.2 Formation of Neural-Organoid Components
After neural induction, pluripotent stem cells form neuroectodermal structures and neural progenitor cells and subsequently develop into three-dimensional neural tissue under suspension or matrix-embedding conditions. Aggregate size, matrix batch, nutrient diffusion, and regionalization signals need to be controlled during culture. Excessively large organoids readily develop central hypoxia and necrosis, which can nonspecifically activate microglia.
4.3 Differentiation of Microglial Progenitor Cells
Pluripotent stem cells can be progressively differentiated into microglial progenitor cells through mesodermal, hematopoietic-like, and myeloid-progenitor stages. M-CSF, IL-34, GM-CSF, TGF-β, and related signals can participate in myeloid-cell survival, CSF1R-associated maturation, and establishment of the homeostatic phenotype. However, specific combinations should be selected according to the differentiation stage, and high CD68 expression or strong phagocytic capacity should not be directly equated with mature homeostatic microglia.
4.4 Exogenous Integration Strategy
The exogenous integration strategy separately prepares brain organoids and microglial progenitor cells before adding the microglial cells to the organoid-culture system at an appropriate time. This method facilitates independent control of the quality and proportion of the two cell populations. However, excessively early integration may interfere with neural-tissue formation, whereas excessively late integration may cause microglia to remain predominantly on the organoid surface.
4.5 Codifferentiation Strategy
Codifferentiation systems preserve or introduce mesoderm-associated cells, allowing microglia to form synchronously during organoid development. This strategy facilitates more continuous developmental interactions, but the proportion and spatial distribution of microglia may vary among batches. Cellular composition should therefore be confirmed through multimarker and single-cell analyses.
4.6 Fusion and Assembly Strategies
Organoid units containing neural cells from different regions or myeloid cells can be fused to form assembloids containing specific brain regions and immune components. This method is suitable for studying microglial migration, brain-region-specific responses, and cross-regional neural networks but requires distinction between effects caused by the fusion interface and genuine disease phenotypes.
5 Microglial Maturation in a Three-Dimensional Microenvironment
5.1 Neural-Cell Signals
Neurons can regulate microglial surveillance, migration, and inflammatory thresholds through CX3CL1, CD200, purinergic signaling, and related pathways. Insufficient neuronal maturity or extensive neuronal death can alter these homeostatic signals and induce nonphysiological microglial activation. Microglial states should therefore be interpreted together with neuronal survival and network maturity.
5.2 Regulation by Astrocytes and the Matrix
Astrocytes regulate the cytokine, lipid, and metabolic-substrate environment and participate in maintaining neural-tissue homeostasis. Laminin, collagen, and other extracellular-matrix components also influence microglial migration and morphology. Changes in matrix composition or stiffness may produce differences in phagocytic and inflammatory phenotypes.
5.3 TGF-β- and CSF1R-Associated Signaling
TGF-β helps maintain homeostatic transcriptional characteristics in microglia, whereas M-CSF and IL-34 support cellular survival and maturation through CSF1R-associated signaling. The effects of different factors are not simply additive. Excessively high concentrations, prolonged treatment, or the absence of neural-tissue signals may shift cells toward a macrophage-like state.
5.4 Nutrient and Oxygen Diffusion
Insufficient nutrient and oxygen diffusion within organoids can cause central necrosis, lactate accumulation, and cellular stress, subsequently inducing microglial accumulation around necrotic regions. Organoid diameter, medium exchange, orbital-shaking conditions, and culture duration should be controlled, and hypoxia-associated responses should be analyzed separately from disease-specific inflammation.
6 Characterization System for MC-HBOs
6.1 Cellular Identity
Microglial identity should be determined using a combination of markers including IBA1/AIF1, P2RY12, TMEM119, CX3CR1, HEXB, and TREM2. IBA1 and CD68 are not microglia-specific markers. Detection of only general myeloid or lysosomal markers cannot distinguish homeostatic microglia, activated microglia, and macrophage-like cells.
6.2 Spatial Integration
Tissue sectioning, confocal optical sectioning, or three-dimensional imaging should be used to confirm that microglia have entered the organoid interior and to analyze their distribution in neuronal layers, necrotic regions, abnormal protein-deposition regions, and on the organoid surface. Detection of overall marker expression in the organoid alone cannot demonstrate effective spatial integration of microglia.
6.3 Cellular Morphology
Homeostatic-like microglia generally have small cell bodies and ramified processes. After inflammatory stimulation or tissue injury, they may exhibit process retraction, enlarged cell bodies, migration, and clustering. Morphological changes can reflect cellular responses but cannot independently determine their functional direction and should be analyzed together with transcriptional states, phagocytic capacity, and inflammatory outputs.
6.4 Phagocytic and Degradative Functions
Apoptotic cells, fluorescent particles, myelin debris, or labeled Aβ can be used to evaluate microglial uptake capacity. Colocalization of cargo with lysosomes and attenuation of fluorescence signals should be further examined. Increased uptake does not necessarily indicate effective clearance. If lysosomal degradation capacity is insufficient, phagocytosed substrates may continue to accumulate intracellularly.
6.5 Inflammatory Responses
Changes in NLRP3, Caspase-1, GSDMD, and inflammatory factors can be measured to analyze microglial responses to abnormal proteins, cellular injury, and exogenous stimuli. Inflammatory responses are time-dependent. Early controlled responses may support clearance, whereas persistent inflammation is more likely to cause synaptic injury and reduced neuronal function.
6.6 Neural-Tissue Function
Model evaluation should also include neuronal numbers, mature markers such as NeuN, synaptic proteins, neurite architecture, and electrophysiological activity. Changes in microglial markers only indicate that the immune component has been affected. Disease-modeling significance can be established only when corresponding structural or functional changes in neural tissue are observed.
Table 2 Major Evaluation Indicators for MC-HBOs
Evaluation Level | Representative Indicators | Major Interpretation |
Microglial identity | IBA1, P2RY12, TMEM119, CX3CR1, and HEXB | Confirm cellular lineage and homeostatic characteristics |
Reactive state | CD68, TREM2, cellular morphology, and migration | Evaluate changes in phagocytic and disease-associated states |
Spatial integration | Three-dimensional localization and intra-/extra-organoid distribution | Exclude cells attached only to the surface |
Phagocytic function | Aβ or particle uptake and lysosomal colocalization | Distinguish uptake, transport, and degradation stages |
Inflammatory pathways | NLRP3, Caspase-1, and GSDMD | Evaluate inflammasome- and pyroptosis-associated responses |
Astrocytes | GFAP and S100B | Evaluate glial-cell interactions and reactive changes |
Neuronal state | NeuN, synaptic proteins, and neurites | Determine neuronal survival and maturation |
Network function | Calcium imaging, multielectrode arrays, and electrophysiology | Evaluate functional consequences of microglial changes |
7 Model Advantages of MC-HBOs
7.1 Human Neural-Immune Interactions
MC-HBOs allow simultaneous observation of neural-cell and microglial responses within the same human genetic background, reducing cross-species signaling differences and enabling distinction between neuron-intrinsic abnormalities and secondary injury mediated by immune cells.
7.2 Developmental Research
Introducing microglia into developing brain organoids allows analysis of their effects on neural progenitor-cell proliferation, neuronal maturation, synapse formation, and network remodeling. This model is particularly suitable for investigating how the timing, proportion, and maturation state of microglia affect brain-developmental outcomes.
7.3 Neuroinflammation Research
Three-dimensional models can preserve local signaling gradients, cell migration, and regions of tissue injury, allowing microglia to develop spatial responses to localized pathological stimuli. Compared with two-dimensional cultures, MC-HBOs are more suitable for evaluating the effects of inflammatory responses on the overall structure and function of neural tissue.
7.4 Patient-Specific Modeling
Patient-derived hiPSCs can be used to construct brain organoids and microglia carrying specific genetic variants, with isogenic correction or gene editing used to establish controls. This approach supports analysis of the cell-type-specific effects of TREM2, APOE, and other risk genes in neural cells and microglia.
7.5 Drug Screening
MC-HBOs can be used to compare the integrated effects of candidate drugs on abnormal protein accumulation, microglial phagocytosis, inflammatory responses, and neuronal survival. Drug efficacy should not be determined solely from reduced inflammatory-factor levels but should also require confirmation of improved abnormal protein clearance, synaptic architecture, and neural-network function.
8 Neurodegenerative Disease Modeling
8.1 Aβ-Induced Models
Aβ monomers, oligomers, or fibrils can be added to organoids to investigate microglial migration, phagocytosis, and inflammatory responses. Different aggregation states have different biological activities. Aβ preparation, preaggregation, concentration, treatment duration, and storage conditions should be clearly defined, and scrambled-peptide or vehicle controls should be included.
8.2 Tau-Pathology Models
Tau-associated models can induce abnormal phosphorylation and aggregation through exogenous Tau proteins, genetic variants, or long-term culture. Evaluation should simultaneously examine Tau levels, microglial uptake, lysosomal degradation, inflammatory responses, and neuronal axonal structure to avoid interpreting increased total Tau directly as insufficient microglial clearance.
8.3 Parkinson’s Disease Models
Introducing microglia into midbrain or dopaminergic-neuron-associated organoids allows investigation of the relationships among α-synuclein, mitochondrial injury, and neuroinflammation. Neurotrophic signals such as GDNF can be used to analyze neuronal survival and protective responses, but their direct neuroprotective effects should be distinguished from indirect effects on microglial states.
8.4 Inflammasome Models
Inflammatory priming combined with a second signal such as ATP can be used to induce the NLRP3 inflammasome, while inhibitors such as MCC950 can be used to validate pathway dependence. Treatment conditions should avoid extensive nonspecific death throughout the organoid, and Caspase-1, GSDMD, and neuronal-injury indicators should be examined simultaneously.
8.5 Drug-Intervention Models
Candidate drugs can target abnormal protein aggregation, phagocytic receptors, inflammasomes, neurotrophic signaling, or microglial metabolism. Drug evaluation should include brain-organoid controls lacking microglia to determine whether the effects arise from direct actions on neural cells or microglia-mediated mechanisms.
9 Products for the Culture, Characterization, and Disease Modeling of Microglia-Containing Brain Organoids
9.1 Products for Three-Dimensional Matrices, Neural Culture, and Signal Regulation
Cat. No. | Product Name | Grade & Purity | Application Positioning |
UltraBio™ Basement Membrane Matrix | BioReagent, Endotoxin Tested, Mycoplasma Free, for Cell culture, Sterile | Used for three-dimensional embedding of brain organoids, extracellular-matrix support, and tissue-structure formation | |
Mouse Laminin from Engelbreth-Holm-Swarm (EHS) sarcoma | BioReagent, Native, ≥95% (SDS-PAGE), 1.0 mg/mL | Used for neural progenitor-cell adhesion, neural-organoid culture, and neural-lineage differentiation | |
Vitronectin from Human Plasma | BioReagent, Native, PBS Only, ≥95% (SDS-PAGE), See COA | Used for iPSC adhesion, expansion, and culture before organoid differentiation | |
N-2 Supplement | Sterile-filtered, BioReagent, for Cell culture, 100X | Used for neural progenitor-cell culture, early neural induction, and construction of defined culture systems | |
Neural-27 Supplement | Sterile-filtered, BioReagent, for Cell culture, Sterile, 50× | Used for long-term brain-organoid culture, neuronal differentiation, and neural-cell survival support | |
Neural-27 Supplement (Minus Vitamin A) | Sterile-filtered, BioReagent, for Cell culture, Sterile, 50× | Used for early neural induction and brain-region patterning requiring restricted retinoic-acid signaling | |
B-27 Supplement (Minus Antioxidants, 50×) | BioReagent, for Cell culture, Sterile, 50× | Used for brain-organoid oxidative-stress, neural-injury, and antioxidant-intervention research | |
B-27 Supplement (Minus insulin, 50×) | BioReagent, for Cell culture, Sterile, 50× | Used for neural differentiation, metabolism, and survival research requiring independent control of insulin signaling | |
ITS-X Supplement (100×) | Sterile-filtered, BioReagent, for Cell culture, 100× | Used to provide insulin, transferrin, and selenium support in serum-free or low-serum organoid culture | |
Y-27632 2HCl | Moligand™, ≥99% | Used to improve cell survival after iPSC dissociation, initial organoid aggregation, passaging, and cryopreservation recovery | |
CHIR 99021 | ≥99% | Used to inhibit GSK-3 and regulate Wnt/β-catenin signaling for control of early lineage determination and neural regionalization | |
SB-431542 | Moligand™, ≥99% | Used to inhibit TGF-β/Activin-associated signaling, promote neural induction, and reduce formation of non-neural lineages | |
XAV 939 | ≥99% | Used to inhibit Tankyrase and Wnt/β-catenin signaling and regulate transitions between neural-differentiation stages | |
DAPT | Moligand™, ≥98% | Used to inhibit Notch signaling and investigate neural progenitor maintenance, neuronal differentiation, and glial-lineage selection | |
Purmorphamine | Moligand™, ≥98% | Used to activate SHH signaling for induction of ventral neural, midbrain, and specific brain-region organoids |
9.2 Products for Microglial Differentiation, Neuronal Survival, and Vascularization
Cat. No. | Product Name | Grade & Purity | Application Positioning |
Recombinant Human TGF-beta 1 Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, High Performance, His Tag, ≥95% (SDS-PAGE) | Used to maintain microglial homeostasis-associated characteristics and investigate TGF-β1-dependent maturation and immune regulation | |
Recombinant Human FGF basic/FGF2/bFGF Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, High Performance, ≥95% (SDS-PAGE) | Used for expansion of iPSCs and neural progenitor cells, early brain-organoid culture, and optimization of differentiation conditions | |
Recombinant Human FGF basic/FGF2/bFGF GMP Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, High Performance, ≥97% (SDS-PAGE & SEC-HPLC) | Used in organoid-culture systems requiring high factor purity, controlled aggregation state, and batch consistency | |
Recombinant Human Noggin Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, Azide Free, His Tag, ≥95% (SDS-PAGE) | Used to inhibit BMP signaling, promote neural induction, and control formation of nontarget lineages | |
Recombinant Human Noggin GMP Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, High Performance, Fc Tag, PBS Only, ≥90% (SDS-PAGE & SEC-HPLC) | Used for neural-differentiation research requiring high culture-factor quality and system reproducibility | |
Recombinant Human Activin A Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, Azide Free, High Performance, His Tag, ≥95% (SDS-PAGE) | Used for early germ-layer induction of iPSCs and research on myeloid- and vascular-progenitor differentiation conditions | |
Recombinant Human/Mouse/Rat Activin A GMP Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, High Performance, ≥97% (SDS-PAGE & SEC-HPLC) | Used for multispecies cell-differentiation systems and organoid models requiring high batch consistency | |
Recombinant Human VEGF 165 Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, High Performance, Sterile, His Tag, PBS Only, ≥98% (SDS-PAGE) | Used for endothelial-cell differentiation, formation of vascular-like structures, and vascularized brain-organoid research | |
Recombinant Human VEGF 165 GMP Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, High Performance, ≥97% (SDS-PAGE & SEC-HPLC) | Used for vascularized organoid culture requiring high VEGF purity and batch consistency | |
Recombinant Human M-CSF GMP Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, High Performance, PBS Only, ≥97% (SDS-PAGE & SEC-HPLC) | Used for myeloid-progenitor differentiation, survival maintenance, and optimization of microglia-like cell-culture conditions | |
Recombinant Human GM-CSF GMP Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, High Performance, PBS Only, ≥97% (SDS-PAGE & SEC-HPLC) | Used for myeloid-progenitor expansion and maturation and for investigating the effects of different combinations of myeloid differentiation factors | |
Recombinant Human IL-34 Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, Azide Free, High Performance, His Tag, ≥95% (SDS-PAGE) | Used to activate CSF1R-associated signaling and support microglial differentiation, survival, and functional maintenance | |
Recombinant Human IL-34 Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, High Performance, ≥95% (SDS-PAGE) | Used for IL-34 concentration optimization, microglial maturation, and comparison of culture conditions | |
Recombinant Human GDNF GMP Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, High Performance, PBS Only, ≥97% (SDS-PAGE & SEC-HPLC) | Used to support dopaminergic-neuron survival and construct Parkinson’s disease-related brain-organoid and neuroprotection models | |
Recombinant Human BDNF GMP Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, High Performance, Sterile, ≥70% (SDS-PAGE) | Used for neuronal survival, synaptic maturation, TrkB signaling, and neural-plasticity research |
9.3 Products for Microglial Characterization, Neuroinflammation, and Disease Modeling
Cat. No. | Product Name | Grade & Purity | Application Positioning |
Iba1 Mouse mAb | Animal Free, Carrier Free, ExactAb™, Azide Free, Validated, High Performance, PBS Only, ≥95% (SDS-PAGE), 1.0 mg/mL | Used to label microglia in organoids and evaluate cell numbers, spatial distribution, and reactive morphology | |
Recombinant CD68 Antibody | Recombinant, ExactAb™, Validated, 0.24 mg/mL | Used to detect phagocytosis- and lysosome-associated activation states and evaluate microglial uptake function | |
Recombinant P2RY12 Antibody | Validated, PBS Only, ≥95% (SDS-PAGE), See COA | Used to detect microglial homeostatic markers and analyze loss of the homeostatic phenotype and reactive transitions | |
GFAP Mouse mAb | Carrier Free, ExactAb™, Azide Free, Validated, High Performance, PBS Only, 1.0 mg/mL | Used to detect astrocyte composition, distribution, and reactive gliosis | |
NeuN Antibody | Recombinant, ExactAb™, Validated, See COA | Used to label mature neurons and evaluate the effects of microglial changes on neuronal survival and tissue architecture | |
Mouse Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) ELISA Kit | BioReagent | Used to detect TREM2 in mouse samples and evaluate microglial phagocytic and disease-associated phenotypes | |
Human NLR Family, Pyrin Domain Containing Protein 3 (NALP3/NLRP3) ELISA Kit | BioReagent | Used to detect NLRP3 levels in human organoids and evaluate changes in inflammasome signaling | |
Caspase-1 Mouse mAb | Carrier Free, ExactAb™, Azide Free, Validated, High Performance, PBS Only, ≥95% (SDS-PAGE), 1.0 mg/mL | Used to analyze Caspase-1-associated inflammasome activation, inflammatory-factor maturation, and pyroptotic responses | |
GSDMD Antibody | Carrier Free, ExactAb™, Azide Free, Validated, High Performance, See COA | Used to detect GSDMD-associated changes and analyze pyroptotic neuroinflammation and plasma-membrane injury | |
Adenosine triphosphate（ATP） | Moligand™, ≥95% | Used as a second signal for inflammasome stimulation and for research on purinergic responses in microglia | |
MCC950 | Moligand™, ≥97% | Used to inhibit the NLRP3 inflammasome and validate pathway dependence of neuroinflammation and neuronal injury | |
minocycline | Moligand™, ≥98% | Used to regulate microglial activation and evaluate microglia-mediated neuroinflammation and injury | |
Amyloid β Protein Fragment 1-42， TFA | ≥95% | Used to prepare Aβ42 monomers, oligomers, or fibrils and establish Alzheimer’s disease-related pathological models | |
Recombinant Human Tau Protein | Animal Free, Carrier Free, Bioactive, ActiBioPure™, His Tag, ≥95% (SDS-PAGE) | Used for research on Tau-protein interactions, aggregation, and microglial responses to Tau pathology |
Microglia-containing brain organoids integrate human neural-tissue architecture, microglial immune responses, and disease-associated stimuli within the same three-dimensional model. By controlling the differentiation stage and integration proportion of microglia and the maturity of the organoids and combining spatial localization, phagocytic degradation, inflammatory signaling, and neural-network functional evaluation, the interpretability of this model in neurodegenerative disease research and drug screening can be improved.
References
[1] Zhang W, et al. Microglia-containing human brain organoids for the study of brain development and pathology. Molecular Psychiatry. 2023;28:96–107. doi:10.1038/s41380-022-01892-1.
[2] Wenzel TJ, Desjarlais JD, Mousseau DD. Human brain organoids containing microglia that have arisen innately adapt to a β-amyloid challenge better than those in which microglia are integrated by co-culture. Stem Cell Research & Therapy. 2024;15.
[3] Mrza MA, He J, Wang Y. Integration of iPSC-Derived Microglia into Brain Organoids for Neurological Research. International Journal of Molecular Sciences. 2024;25. doi:10.3390/ijms25063148.
[4] Haenseler W, Rajendran L. Concise Review: Modeling Neurodegenerative Diseases with Human Pluripotent Stem Cell-Derived Microglia. Stem Cells. 2019;37:724–730.
For more related articles, please see below:
[1] Microglia primary culture experiment
[2] Alzheimer’s Disease Signaling
[3] Experiments in the production of a model of Parkinson's disease
[4] Exendin-4 and Alzheimer’s Disease
[5] Four Major Classifications and Seven Key Mechanisms of Neuroinflammation
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