Condensation‐Driven Chondrogenesis of Human Mesenchymal Stem Cells within Their Own Extracellular Matrix: Formation of Cartilage with Low Hypertrophy and Physiologically Relevant Mechanical Properties
Abstract
Mesenchymal stem cells (MSCs) represent a promising cell source to regenerate injured cartilage. In this study, MSCs are cultured under confluent conditions for 10 days to optimize the deposition of the extracellular matrix (mECM), which will serve as the scaffold to support MSC chondrogenesis. Subsequently, the MSC‐impregnated mECM (MSC‐mECM) composite is briefly treated with trypsin, allowing the MSCs to adopt a round morphology without being detached from their own mECM. The constructs are then cultured in a chondrogenic medium. Interestingly, after trypsin removal, the treated MSCs undergo an aggregation process, mimicking mesenchymal condensation during developmental chondrogenesis, specifically indicated by peanut agglutinin staining and immunodetectable N‐cadherin expression, followed by robust chondrogenic differentiation. In comparison to conventional pellet culture, chondrogenically induced MSC‐mECM displays a similar level of chondrogenesis, but with significantly reduced hypertrophy. The reparative capacity of the MSC‐mECM derived construct is assessed using bovine cartilage explants. Mechanical testing and histology results show that engineered cartilage from MSC‐mECM forms better integration with the surrounding native cartilage tissue and displays a much lower hypertrophic differentiation than that from pellet culture. Taken together, these findings demonstrate that MSC‐mECM may be an efficacious stem cell‐based product for the repair of hyaline cartilage injury without the use of exogenous scaffolds.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 04, 2019
- Source ID
- 10.1002/adbi.201900229
Entities
People
- Biao Kuang
- Caitlin Lucas
- Hang Lin
- He Shen
- Rocky Tuan
- Yuanheng Yang
- Yuwei Liu
- Zixuan Lin
Organizations
- Central South University
- The Chinese University of Hong Kong
- United States Department of Defense
- University of Pittsburgh