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Engineering hyaline cartilage from mesenchymal stem cells with low hypertrophy potential via modulation of culture conditions and Wnt/β-catenin pathway.
- Source :
-
Biomaterials . Feb2019, Vol. 192, p569-578. 10p. - Publication Year :
- 2019
-
Abstract
- Abstract Mesenchymal stem cells (MSCs) represent a promising cell source to regenerate articular cartilage, but current chondroinduction protocols, commonly using transforming growth factor-β (TGFβ), lead to concomitant chondrocytic hypertrophy with ossification risk. Here, we showed that a 14-day culture of MSC-laden hyaluronic acid hydrogel in the presence of TGFβ, followed by 7 days culture in TGFβ-free medium, with the supplement of Wnt/β-catenin inhibitor XAV939 from day 10–21, resulted in significantly reduced hypertrophy phenotype. The stability of the hyaline phenotype of the MSC-derived cartilage, generated with a standard protocol (Control) or the optimized (Optimized) method developed in this study, was further examined through intramuscular implantation in nude mice. After 4 weeks, constructs from the Control group showed obvious mineralization; in contrast, the Optimized group displayed no signs of mineralization, and maintained cartilaginous histology. Further analysis showed that TGFβ treatment time affected p38 expression, while exposure to XAV939 significantly inhibited P-Smad 1/5 level, which together resulted in decreased level of Runx2. These findings suggest a novel treatment regimen to generate hyaline cartilage from human MSCs-loaded scaffolds, which have a minimal risk of eliciting endochondral ossification. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MESENCHYMAL stem cells
*WNT signal transduction
*CARTILAGE regeneration
Subjects
Details
- Language :
- English
- ISSN :
- 01429612
- Volume :
- 192
- Database :
- Academic Search Index
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 134048571
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2018.11.036