Harnessing the Regenerative Characteristics of Meniscus Superficial Zone Cells

The meniscus is a semilunar fibrocartilaginous structure that is critical for knee joint function. Tears in the knee meniscus present a significant clinical burden due to the limited endogenous healing capacity. Superficial meniscus cells are thought to play a critical role in meniscus injury response, and migrate to the injury site, proliferate rapidly, and in some instances can deposit repair tissue. However, this repair tissue lacks structure organization and integrity of the native tissue, and so understanding of and optimizing the activities of these superficial cell behavior may aid in the development of new therapeutic interventions towards functional meniscus repair. This study explores the distinct behavior and phenotype of superficial layer cells on multiple scales using transcriptomic profiling, migration, and proliferation assays, mechanosensation analysis, and traction force microscopy. After, the matrix deposition potential of superficial cells was assessed on electrospun nanofibers. Here, we show at the transcriptional level that superficial cells are most similar to those of the meniscus body, while also expressing a subset of genes consistent with the adjacent synovium. These cells also show a decreased response to changes in microenvironmental stiffness and generate lower traction forces but migrate faster and proliferate at higher rates in low-stiffness environments compared to body cells. Notably, in 3D culture, superficial cells can produce functional tissue with mechanical properties comparable to that produced by meniscus body cells. Overall, this body of work elucidates the regenerative potential of superficial meniscus cells, providing new insights for that might be leveraged in future tissue engineering and drug delivery approaches to improve meniscus repair.

Author dc:creator

• Assi, Sereen, S.F.

Advisors dc:contributor.advisor

• Cohen, Yale
• Loo, Boon, T

• Engineering
• Medicine and Health Sciences
• Biology

Language dc:language.iso

en

Repository record dc:identifier.uri

https://repository.upenn.edu/handle/20.500.14332/60458

OAI identifier oai:identifier

oai:repository.upenn.edu:20.500.14332/60458