Pellet coculture of osteoarthritic chondrocytes and infrapatellar fat pad-derived mesenchymal stem cells with chitosan/hyaluronic acid nanoparticles promotes chondrogenic differentiation

Shu Huang,Xiongbo Song,Jingfang Xiao,Weinan Zeng,Xiaoyuan Gong,Tao Li,Cheng Chen,Liu Yang,Yemiao Chen

doi:10.1186/s13287-017-0719-7

Shu Huang, Xiongbo Song + Show 7 more

Open Access

https://doi.org/10.1186/s13287-017-0719-7

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Abstract

BackgroundCell source plays a key role in cell-based cartilage repair and regeneration. Recent efforts in cell coculture have attempted to combine the advantages and negate the drawbacks of the constituent cell types. The aim of this study was to evaluate the chondrogenic outcome of articular chondrocytes (ACs) and infrapatellar fat pad (IPFP)-derived mesenchymal stem cells (MSCs) in direct coculture.MethodsACs and IPFP MSCs from the same patients with knee osteoarthritis (OA) were cocultured in monolayer and in pellets. The monocultures of each cell type were also used as controls. Morphological and histologic analysis, immunofluorescence staining, reverse transcription-polymerase chain reaction, and enzyme-linked immunosorbent assay were performed to characterize the chondrogenic differentiation of cocultures. Furthermore, the effects of chitosan/hyaluronic acid (CS/HA) nanoparticle exposure on the chondrogenesis of cocultures were examined.ResultsIn both monolayer and pellet coculture, the hypertrophy of MSCs and the inflammatory activities of ACs were inhibited, although the chondrogenic production in coculture was not promoted compared with that in monoculture. In addition, the exposure of CS/HA nanoparticles to pellet coculture improved the production of type II collagen and aggrecan.ConclusionsWe demonstrate for the first time that pellet coculture of ACs and IPFP MSCs with CS/HA nanoparticles could promote chondrogenic outcome while preventing the inflammatory status of ACs and the hypertrophic differentiation of MSCs. These findings suggest that the combination of ACs, IPFP MSCs, and CS/HA might be useful in cartilage repair in knee OA.

Highlights

Cell source plays a key role in cell-based cartilage repair and regeneration
Results of this study indicate the possibility of developing a one-step cartilage repair by using a combination of infrapatellar fat pad (IPFP) Mesenchymal stem cell (MSC), Articular chondrocyte (AC), and CS/Hyaluronic acid (HA) NPs for patients with knee OA
We found that the concentration of both IL-1β and MMP-13 was highest in monoculture of ACs as expected since P0 osteoarthritic chondrocytes without passaging were used

Summary

Introduction

Cell source plays a key role in cell-based cartilage repair and regeneration. The aim of this study was to evaluate the chondrogenic outcome of articular chondrocytes (ACs) and infrapatellar fat pad (IPFP)derived mesenchymal stem cells (MSCs) in direct coculture. Significant research efforts are aimed at producing engineered cartilage as a cell-based approach for articular cartilage repair [4,5,6]. The most commonly used cell sources in cartilage tissue engineering and regenerative medicine are native cartilage cells, or autologous chondrocytes, but they undergo rapid dedifferentiation during in-vitro expansion, and result in the formation of fibrocartilage with inferior mechanical properties [7, 8]. Mesenchymal stem cells (MSCs) have been widely investigated as an alternative cell source in cartilage regeneration due to their great chondrogenic potential [9, 10]. MSCs with the current chondrogenic differentiation protocol usually result in the hypertrophic phenotype and calcification [11, 12]

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