Predictive Models for Neuroscience Research

Develop Predictive Neural Models

For neuroscientists, the quest for truly predictive neural models has its challenges given the brain is a very complex organ comprised of many diverse cell types, complex cell-tocell interactions and intricate signaling pathways. But new breakthroughs using molecular tools and stem cell models are now better able to mimic the physiology of the brain to help explore the origins of neurological disorders and disease. With the help of these models new treatments and even personalized therapies are being created.

Creating predictive neural models involves three processes:

 

Use this guide to discover each step and DEVELOP the predictive neural model you’ve been waiting for.

SELECT > Cell type

Cells that mimic the physiology of the human brain and the bloodbrain barrier (BBB) will produce more relevant and accurate results. Count on our full offering of stem cells, primary cells and other novel cell lines that are well characterized and designed specifically for neuroscience research.

CHALLENGE

Creation of more physiological in vitro culture systems that mimic in vivo environments.

SOLUTION

Neural Cell Lines
The use of immortalized cell lines has many advantages including the capability of long-term growth and ease to cultivate. Additionally, when neural stem cells (NSCs) are used they have an added benefit of selfrenewal and differentiation along specific pathways to generate physiological relevant neuronal and glial cell types of the central nervous system (CNS).
 

Product No. Description
Mouse Cell Lines
SCC116 GT1-7 Mouse Hypothalamic GnRH Neuronal Cell Line
SCC049 Mouse Cranial Neural Crest Cell Line O9-1
SCR029 Mouse Cortical NSC, 1 million cells
SCR031 Mouse Spinal Cord NSC, 1×106
Rat Cell Lines
SCC048 N27 Rat Dopaminergic Neural Cell Line
SCR022 Adult Rat Hippocampal, 1×106
SCC103 HAPI Rat Microglial Cell Line
Human Cell Lines
SCC035 Human iPSC Derived Neural Progenitors
SCC066 Blood Brain Barrier hCMEC/D3 Cell Line
SCR600 Human Oligodendrocyte Differentiation Kit
SCC007 ReNcell CX Human Neural Progenitor Cell Line
SCC008 ReNcell VM Human Neural Progenitor Cell Line
SCR055 ENStem Human Neural Progenitor Expansion Kit

Product Highlight

ReNcell® VM Human Neural Stem Cell (NSC) Line
Product No. SCC008
As seen in Nature. 2015 Jul;10(7): 985–1006

Immortalized human neural progenitor cell line with the ability to readily differentiate into neurons and glial cells, making them the ideal platform for neuroscience research.

  • Consistent and dependable neural stem cell culture
  • Immortalized to produce a robust and consistent NSC culture
  • Offers phenotype and genotype stability
  • Includes multipotential neuronal and glial differentiation capacity
  • Culture in optimized defined serum-free media

Ask about the NEW protocol to make a 3D cell model of Alzheimer’s Disease using ReNcell® VM cells.

SELECT > Cell type

CHALLENGE

A need for more physiological in vitro culture systems that are more comparable to in vivo environments.

SOLUTION

Primary Cells
Closely mimic in vivo conditions with primary neuronal cultures that are derived directly from tissue and maintain physiological relevance. We have partnered with Cell Applications Inc., who is a leading authority and global provider of primary human and animal cell types, to provide greater than 100 different human and animal cells, cited extensively in original, peer-reviewed research articles and patents.

Rat Primary Cells

Product No. Description
Rat Astrocytes
R882-05n Rat Astrocytes: RA (Cryovial)
Rat Neurons
R882N Rat Cortical Neurons: RCoN
R8820N-05 Rat Dorsal Root Ganglion Neurons: RDRGN
R888N-10 Rat Hindbrain Neurons: RHbN
R886N-10 Rat Hippocampal Neurons: RHiN
R8810N-10 Rat Midbrain Neurons: RMbN
R8814N Rat Spinal Cord Neurons: RSpN
R8812N-10 Rat Striatal Neurons: RStN

SELECT > Cell type

CHALLENGE

Authenticated cell lines that are free of contamination (e.g. other cell lines and microbes) are of the utmost importance to safeguard reproducibility.

SOLUTION

Culture Collection Cell Lines
We have formed a working partnership with The European Collection of Authenticated Cell Cultures (ECACC), a world leader and recognized expert in the maintenance, cultivation and distribution of a unique repository of over   1,300 validated cells. Cell lines obtained from ECACC are tested for viability (plating efficiency and cell density), morphology, sterility, mycoplasma contamination and authenticity, offering the most diverse and validated selection available so you can ensure reproducible results.

ECACC Cells

Product No. Description  
94030304 SH-SY5Y cells,
Human Neuroblastoma


The SH-SY5Y cell line has become a popular cell model for PD research because this cell line possess many characteristics of DAergic neurons. For example, these cells express tyrosine hydroxylase and dopamine-betahydroxylase, as well as the dopamine transporter. Moreover, this cell line can be differentiated into a functionally mature neuronal phenotype in the presence of various agents. Upon differentiation, SH-SY5Y cells stop proliferating and a constant cell number is subsequently maintained.
89081402 U-87 MG human glioblastoma astrocytoma U87MG cells express the astrocyte cell marker glial fibrillary acidic protein (GFAP) and are widely used as an in vitro astrocyte model.
89121404
Neuro 2A Mouse Albino Neuroblastoma Neuro 2A (N2a) is a mouse neural crest-derived cell line that has been extensively used to study neuronal differentiation, axonal growth and signaling pathways.
92090903 ND7/23 Mouse Neuroblastoma X Rat Neuron The ND7-23 immortalized rat dorsal root ganglion (DRG)-mouse N18Tg2 neuroblastoma hybrid cell line has shown great utility for transient and stable expression of exogenous ion channels and receptors in a native milieu, yielding useful fluorescence and electrophysiology assays for academic and drug discovery applications.

See more at SigmaAldrich.com/neuro-ecacc

CREATE > Genetic Modification

The ability to modify genes (e.g. edit or knockout genes) in cell models enables the discovery and study of novel neurological pathways. Count on our extensive portfolio of CRISPRs, ZFNs, and other technologies to engineer the predictive neural model you need.

CHALLENGE

Neural models are difficult to generate and manipulate. Novel tools and techniques are needed to overcome a variety of barriers.

challenges to overcome variety of barriers

SOLUTION

Genome Editing Tools
The recent advancement of functional genomic tools, like CompoZr® ZFN and CRISPR, allows researchers to knock-out, knock-in and modify genes in order to create their ideal cell model, revealing novel relationships between genes and neurological phenotypes.

CRISPR
The advent of CRISPR has been timed perfectly with a reduction in DNA sequencing costs and a recent boom in neuroscience research. Through the democratization of genome editing researchers worldwide are now able to uncover genes implicated in neural development and disease whose relationship was previously unknown. A greater depth in the understanding of the pathways involved in Alzheimer’s, schizophrenia, and a host of other neurological diseases is now a reality. In addition to using CRISPR to study cultured cells, a sizable and growing number are using this tool to generate transgenic animals enabling heretofore impossible interrogations of the brain and complex neural tissues.

Custom Research Models

Cell Design Studio
Our Cell Design Studio team is made up of experienced, dedicated scientists who work to provide solutions for your neural model needs. With in-house access to CRISPR, zinc finger nuclease, and shRNA technologies, our experts can rapidly generate knock-outs, knock-ins, and gene modifications in a variety of mammalian cell lines. Our ultimate goal is to provide you not with a cell line, but with a solution. We focus on the cell engineering details so you can focus on the science.

custom research models

Cellular reprogramming technologyTechnology Highlight

Cellular Reprogramming

Simplicon™ RNA Reprogramming Technology
Product  No. SCR550

Our reprogramming technology utilizes a selfreplicating RNA strand allowing efficient, virusfree reprogramming generating high numbers of induced pluripotent stem cells (iPSCs) with a single transfection step. Use Simplicon RNA reprogramming technology with efficient media and supporting products to provide a complete solution for modeling neurological diseases using an iPS cell model system.

See more at SigmaAldrich.com/neuro-simplicon

OPTIMIZE > Growth and Consistency

An optimized culture environment is extremely important for the reproducibility of your neural model. Depend on our well characterized specialty medias, growth factors, sterile filtration systems and 3D culture products to provide the consistency you need to advance your neuroscience research.

Technology Highlight

Neurite Outgrowth

AXIS® Axon Isolation System
Use our AXIS platform for the most advanced tool to study neurite outgrowth. This slidemounted microfluidic two-chamber system enables the deposition and culture of neural cells and the spatially controlled addition of growth factors, toxins, and other reagents. Neurite outgrowth is restricted to narrow, parallel channels, and the resultant outgrowth or collapse behavior is easily observed under a microscope. The result is a powerful platform for the study of somas, neurite outgrowth, and synapse formation.

Fluorescent image showing the N1E-115

N1E-114 cells were loaded in the lower channel and cultured for 5 days in differentiation media. The cells were then fixed and stained with DAPI (blue) and with the neuronal cell stain MAB23D0X (green).

A) Fluorescent image showing the N1E-115 cells differentiating through the microgrooves of the AXIS® device. Note that the cell bodies (somas) are entirely contained on one side of the device and only the neurites are extended through the microgrooves into the other channel. B) Higher resolution white light image of the cells and device. C) Corresponding fluorescent image. D) Overlay of images B and C to verify that the neurites extend through the microgrooves only.
 

  AXIS® Axon
Isolation Device
Microgroove Length
Tissue Culture Ready (TC) Plasma Bonded (PB) Plasma Bonded to
Confocal dishes (PBC)
Optimal Use   Ready-to-use devices. Just mount on slide and go. Good for slide or coverslip users. Pre-sealed to glass slides to prevent leakage. Excellent for beginners. Pre-sealed to coverslip glass culture dishes for confocal imaging from bottom.
Short experiments or maximal growth in axonal compartment 150 μm,
4 well
AX15010TC AX15005PB AX15005PBC
Most common axonal studies 450 μm,
4 well
AX45010TC AX45005PB AX45005PBC
More complex studies where 2 sets of microgrooves are needed 500 μm,
6-well
AX50010TC AX50005PB AX50005PBC
Longer axonal growth or transport studies 900 μm,
4 well
AX90010TC

OPTIMIZE > Growth and Consistency

CHALLENGE

Creating similar environmental conditions that exist in nature is essential for relevant neural models.

SOLUTION

Growth Environment

3D Cell Culture

Cells in their natural environment have constant interactions with the extracellular matrix (ECM) and other cells, regulating complex biological functions like cellular migration, apoptosis, or receptor expression. Most of these interactions are lost, or significantly reduced, in 2D cell culture. By culturing cells in the presence of ECM components, particularly ECM proteins like collagen, laminin or fibronectin, they allow you to recapitulate a 3D cell culture and produce a more predictive neural model. CHALLENGE Creating similar environmental conditions that exist in nature is essential for relevant neural models.

See more at SigmaAldrich.com/neuro-3dpcell

 

SOLUTION

Growth Environment

Media and Growth Factors

To closely represent the in vivo environment of neural cells correct biological conditions are essential. Achieve relevant growing conditions with our well cited, sterile media options optimized for neuroscience research. And get consistent cell proliferation and differentiation with our high quality growth factors to achieve a more neurological phenotype.

Media and Growth Factors

Product No. Description
G0800 GS21™ Supplement (50X), Serum-free Natural Media Supplement
N3100 NeuralQ™ Basal Medium
S3194 Stemline® Neural Stem Cell Expansion Medium
SCR603 Human ES/iPS Neurogenesis Kit
SCR135 Human Dopaminergic Neurogenesis Kit
SCM005 ReNcell NSC Maintenance Media
SCM110
Human ES/iPS Neural Induction Medium
SCM111 Human ES/iPS Neuronal Differentiation Medium
B3795 Brain-derived neurotrophic factor human
F0291 hBFGF FGF-Basic
GF446 HumanKine® Thermostable bFGF, Human Recombinant
V7259 Vascular Endothelial Growth Factor human
G1777 Glial Cell Line-derived Neurotrophic Factor human

 

OPTIMIZE > Growth and Consistency

CHALLENGE

A simple, reproducible method for the critical steps of accurately preparing cells and media.

SOLUTION

Sterile Filtration
Establishing a successful neural cell culture begins with optimizing cells and media with the highest standards. From challenging neuronal cell lines to minimal sample availability, count on our sterile filtration products to provide quality and reproducibility to your media and supplements.

  • Stericup® and Steritop® Filter Units
    Remove undesirable contaminants and sterilize your media with our high-flow rate Stericup® and Steritop® filters. This compact, stable and easy to grip system allows for very low protein binding with a wide range of membranes and volume capacities. As an added precaution it has recessed threads on the cap to safeguard against contaminants. You can also use Steritop® bottle-top devices with your own sterile capture flask or bottle.
  • Millex® Syringe Filters
    Ensure faster flow rate for greater throughput, with maximum recovery of soluble proteins using our Millex® syringe filters. These color-coded syringe filters provide instant visual identification, reducing the risk of confusing similar-sized devices on the bench.
Product No. Description Size
Stericup® Filter Units
SCGPU05RE 0.22 μm Millipore Express Plus (PES) 500 mL – low protein binding
SCGVU05RE 0.22 μm Durapore (PVDF) 500 mL – very low protein binding
Steritop® Filter Units
SCGPS05RE 0.22 μm Millipore Express Plus (PES) 500 mL – 33mm threads
SCGVT05RE 0.22 μm Durapore (PVDF)
500 mL – 45mm threads
Millex® Syringe Filters
SLGP033RB 0.22 μm Millipore Express Plus (PES) 33 mm – 250 pack
SLGV033RB 0.22 μm Durapore (PVDF) 33 mm – 250 pack
Steriflip® Filter Units
SCGP00525 0.22 μm Millipore Express Plus (PES) 50 mL – 25 pack
SE1M179M6 0.22 μm Durapore (PVDF) 50 mL – 25 pack
SCNY00020 20 μm nylon net 50 mL – 25 pack