Human chondrogenic paraxial mesoderm, directed specification and prospective isolation from pluripotent stem cells

Area of Science:

• Stem cell biology
• Regenerative medicine
• Developmental biology

Background:

• Directed specification of chondrogenic paraxial mesoderm from human pluripotent stem cells (hPSCs) remains a challenge.
• Existing methods lack efficient isolation of specific chondrogenic progenitor populations.

Purpose of the Study:

• To achieve directed specification and prospective isolation of chondrogenic paraxial mesoderm progeny from hPSCs.
• To evaluate the chondrogenic potential of these derived cells for cartilage engineering and repair.

Main Methods:

• Utilized a chemically defined medium with specific signaling pathway modulators (WNT activator, BMP-inhibitor, Nodal/Activin/TGFβ controller).
• Generated KDR(-)PDGFRα(+) progeny expressing paraxial mesoderm genes and MIXL1-GFP reporter.
• Isolated GFP(+) cells and assessed chondrogenic differentiation potential in response to PDGF, TGFβ, and BMP in micromass culture.

Main Results:

• Successfully generated and isolated KDR(-)PDGFRα(+) paraxial mesoderm-like cells from hPSCs.
• These cells exhibited robust chondrogenic activity, forming hyaline-like cartilage in serum-free conditions.
• Compared to adult mesenchymal stem/stromal cells, hPSC-derived cells demonstrated superior chondrogenic response and cartilage quality.

Conclusions:

• hPSC-derived KDR(-)PDGFRα(+) paraxial mesoderm-like cells are a promising source for engineered cartilage.
• These cells hold significant potential for applications in cartilage repair strategies.
• The developed method offers a novel approach for generating specific chondrogenic progenitor populations from hPSCs.