Formation of functionally robust human neocartilage from multiple donors using highly expanded costochondral cells.

Area of Science:

• Tissue Engineering
• Regenerative Medicine
• Biomaterials Science

Background:

• Successful allogeneic tissue-engineered neocartilage requires abundant functional cells.
• Human costal cartilage is a promising cell source, but donor variability and passaging effects are unclear.

Purpose of the Study:

• Investigate functional properties of hyaline-like neocartilage from high-passage human costochondral cells.
• Identify predictive markers for neocartilage functional properties.

Main Methods:

• Utilized a cell banking system for seven donors, creating master and working cell banks.
• Fabricated P5 and P9 constructs using conservative chondrogenic passaging, aggregate rejuvenation, and self-assembly.
• Correlated cell morphology and gene expression with mechanical and biochemical properties.

Main Results:

• Aggregate rejuvenation effectively restored hyaline cartilage phenotype at P9, similar to P5, with significant chondrogenic gene upregulation.
• Cells from younger donors (<=3 months) expanded more than older donors (9-14 years).
• Identified gene expression markers (e.g., ACAN, Chm-1, MIA, SOX9, MMP13) that predict neocartilage mechanical and biochemical properties.

Conclusions:

• Extensively passaged human costochondral cells demonstrate translational potential for neocartilage engineering.
• Donor screening is crucial for optimizing neocartilage functional properties.
• Gene expression profiling post-rejuvenation is a valuable tool for predicting neocartilage outcomes.