Home Cell Biology Isolation of CD133+ Liver Stem Cells for Clonal Expansion
Cell Biology JoVE (Open Access) Citable · DOI

Isolation of CD133+ Liver Stem Cells for Clonal Expansion

DOI: 10.3791/3183-v
What you'll learn
  • Isolate CD133+ liver stem cells from whole murine liver tissue using enzymatic digestion and flow cytometry.
  • Perform parenchymal/non-parenchymal cell separation and hematopoietic cell depletion from liver preparations.
  • Execute single-cell sorting and establish clonal expansion cultures from enriched stem cell populations.
  • Analyze and validate CD133+ cell populations using flow cytometry-based cell isolation techniques.
Protocol

Here we describe the isolation of CD133 expressing liver stem cells and cancer stem cells from whole murine liver, a process that requires tissue digestion, cell enrichment, and flow cytometry isolation. We include methods for advanced single cell isolation and clonal expansion.

Difficulty
advanced
Total time
~4-6 hours per mouse (tissue harvest through cell sorting; clonal expansion requires 1-2 weeks culture)
Model organism
Mouse (murine liver)
Biosafety
BSL-1

Steps

1
Separate parenchymal and non-parenchymal liver cells

Digest whole murine liver tissue to obtain parenchymal hepatocytes and non-parenchymal cell fractions. This enzymatic dissociation step is critical for accessing stem cell populations within the liver microenvironment.

▶ 01:45
2
Perform red blood cell lysis

Apply red cell lysis buffer to remove erythrocytes and improve cell population purity before downstream enrichment. This step reduces background contamination in subsequent flow cytometry.

▶ 04:51
3
Deplete CD45+ hematopoietic cells from non-parenchymal fraction

Use CD45-targeted immunomagnetic depletion to remove hematopoietic lineage cells and enrich for rare stem cell populations. This negative selection step increases CD133+ stem cell representation in the final population.

▶ 05:51
4
Isolate CD133+ cells by flow cytometry sorting

Apply flow cytometric gating to identify and sort CD133-positive liver stem and cancer stem cells into pure populations. Single-cell sorting enables clonal expansion from individual cells.

▶ 07:31
5
Validate sorted cell populations and expand clones

Confirm CD133+ cell identity through post-sort analysis and establish single-cell derived clonal cultures. Representative sorting efficiency and purity data validate the isolation strategy.

▶ 09:03
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