| Beitragstitel | SPHEROIDS DERIVED FROM HUMAN NASAL CHONDROCYTES AS PROMISING CELL SOURCE FOR NUCLEUS PULPOSUS REPAIR |
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| Beitragscode | P19 |
| Autoren | |
| Präsentationsform | Poster |
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| Abstract |
Introduction. Cell-based therapy for degenerative disc disease (DDD) still faces limitations associated with cell engraftment in a harsh microenvironment. Recent studies show that spheroids (multi-cellular aggregates with self-produced matrix) may enhance cell adhesion, resistance, and function. Nasal chondrocyte (NC) spheroids (NCS) could be an excellent source for nucleus pulposus (NP) repair, as NC survive in harsh microenvironments better than traditionally used MSCs. We aim this study at analysing the therapeutic potential of NCS for NP repair, namely their capacity for injectability, matrix accumulation, and tissue integration. Methods. Human NCS were fabricated for 1-7 days with or without standard chondrogenic supplements. NCS size, shape, injectability, elastic modulus, biochemical content, and gene/protein expression were evaluated. The fusion NP model was generated from human NP spheroids formed for 14 days. NCS-NPS fusion kinetics and viability were determined in DDD-mimicking conditions (inflammation, hypoxia, acidity, low glucose). The effect of NCS injection through a clinically relevant spinal needle into an ex vivo cultured bovine intervertebral disc (IVD) were investigated. Results. Non-adhesive technology allowed the fabrication of NCS compatible with a spinal needle (22G). Chondrogenic supplements time-dependently increased E of NCS in correlation with gene/protein expression of collagen (p < 0.05), when compared to medium without supplements that produced NCS with stable elastic modulus (E, ~5 kPa). Neither NCS-NPS fusion nor viability were impaired by the DDD mimicking conditions. The injection into the bovine IVD did not disrupt the structural integrity of the NCS. Conclusion. Our data indicate that NCs cultured as spheroids can produce NP-compatible matrix, develop biomechanical properties similar to NP tissue, and possess the capacity to integrate within NP microenvironment. Moreover, specific NCS properties are potentially tunable by culture supplements. These results need to be verified in a whole disc organ culture bioreactor, towards demonstration of the functionality of NC for NP repair. |