Stem Cells

P175 - Protective paracrine effect on chondrocytes when co-cultured with mesenchymal stem cells in a hyaluronic acid hydrogel in vitro

Corresponding Author
Disclosure
No Significant Commercial Relationship
Presentation Topic
Stem Cells
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Abstract

Purpose

Purpose

The aim of the present study was to investigate cell viability and paracrine effects of MSCs on human chondrocytes in an inflammatory co-culture assay. We hypothesized that MSCs immobilized in a hyaluronic acid (HA) hydrogel exerted protective paracrine effects on human chondrocytes when exposed to interleukin-1beta (IL-1b) induced inflammatory environment.

Methods and Materials

Methods and Materials

Non-osteoarthritic human chondrocytes where co-cultured in biphasic wells with human MSCs immobilized in a divinyl sulfone crosslinked HA (500- 749 KDa) hydrogel (HyA) without physical contact between the two cell types. We investigated the chondrocyte response in an IL-1b induced inflammatory environment in four groups: 1) chondrocytes 2) chondrocytes and HyA 3) chondrocytes and MSCs 4) chondrocytes and HyA-immobilized MSCs. Follow-up times were day 3, 7 ,14, and 28. Relative gene expressions of aggrecan, SOX9, MMP-13 and ADAMTS-5 were measured. The unfolded protein response (UPR) was examined as a surrogate marker of cellular stress and the viability was studied using Hoechst staining.

Results

Results

MSC viability was maintained in the hydrogel for up to 28 days. In chondrocytes co-cultured with MSCs or MSCs immobilized in HyA we found significant up-regulation of SOX9 at day 7, 14 and 28 and a significant down-regulation of ADAMTS-5 at day 14 and 28 compared with controls and HyA alone (p < 0.05). The UPR was down-regulated (1-3 fold) in co-cultures with MSCs but results were not significant.

Conclusion

Conclusions

We show that human MSCs can be immobilized in HyA and survive for up to 28 days and that MSCs with or without HyA exert protective paracrine effect on non-osteoarthritic human chondrocytes in an IL1-b induced environment.

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