Method Article

Immunostaining of Cells Encapsulated in a 3D Hydrogel System

July 8th, 2025

In This Article

Abstract

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Source: LeSavage, B. L., et al. Production of Elastin-like Protein Hydrogels for Encapsulation and Immunostaining of Cells in 3D. J. Vis. Exp. (2018).

This video demonstrates a technique for immunostaining cells encapsulated in a 3D hydrogel. The hydrogel culture containing neural progenitor cells is fixed, permeabilized, and treated with a blocking solution to prevent non-specific immunostaining. A primary antibody cocktail is added to bind specific proteins, followed by fluorescently labeled secondary antibodies and a nuclear stain. The sample is then mounted on a slide and observed under a confocal microscope.

Protocol

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1. Cell Encapsulation in 3D Elastin-like Protein (ELP) Hydrogels

  1. Preparation of silicone molds
    1. Use a biopsy punch with the desired diameter to create holes in a 0.5 mm thick silicone sheet and cut out a square around each hole. Repeat for the number of molds desired.
      ​NOTE: The diameter and thickness of the molds can be adjusted for the particular application and cell culture conditions. In practice, for cell cultures of 50 x 106 cells/mL, 0.5 mm thick molds with 4 mm and 5 mm diameters are recommended for sufficient DNA/RNA and protein extraction, respectively. For imm....

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Disclosures

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No conflicts of interest declared.

Materials

List of materials used in this article
NameCompanyCatalog NumberComments
Cell Encapsulation in 3D ELP Hydrogels
0.22 μm syringe filtersMilliporeSLGV004SL
0.5 mm thick silicone sheetElectron Microscopy Science70338-05
24-well tissue culture platesCorning353047
Disposable Biopsy Punch (2 mm)Integra Miltex33-31
Disposable Biopsy Punch (4 mm)Integra Miltex33-34
Disposable Biopsy Punch (5 mm)Integra Miltex33-35
Dulbecco’s phosphate buffered saline (DPBS)Corning21-031-CM
No. 1 12 mm glass coverslipsThermo Fisher Scientific12-545-80
Tetrakis(hydroxymethyl)phosphonium chloride (THPC)Sigma-Aldrich404861-100ML
0.5% Tryspin/EDTAThermo Fisher15400054
Immunocytochemistry of Cells in 3D ELP Hydrogels
16% (w/v) Paraformaldehyde (PFA)Electron Microscopy Sciences15701
Bovine Serum Albumin (BSA)Roche3116956001
DAPI (4',6-Diamidino-2-Phenylindole, Dihydrochloride)Molecular ProbesD1306
Donkey SerumLampire Biological Labs7332100
Goat anti-mouse Secondary Antibody (AF488)Molecular ProbesA-11017
Goat anti-rabbit Secondary Antibody (AF546)Molecular ProbesA-11071
Goat SerumGibco16210-072
Mouse Nestin Primary AntibodyBD Pharmingen556309
Mouse Sox2 Primary AntibodyCell Signaling Technology23064S
Nail PolishElectron Microscopy Sciences72180
Triton X-100Sigma-AldrichX100-100ML
Vectashield Hardset Mounting MediumVector LabsH-1400

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Tags

3D Hydrogel SystemCell EncapsulationImmunostaining TechniqueConfocal MicroscopyPrimary AntibodySecondary AntibodyNuclear StainHydrogel FixationPermeabilization SolutionBlocking Solution

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