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

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.

Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine

“…CS derivative carboxymethyl-CS in a dose-dependent manner reduced the inflammatory profile of primary rat chondrocytes by reducing iNOS expression and upregulating the anti-inflammatory cytokine IL-10 in vitro [87]. In another study, the addition of hyaluronic acid-CS NPs to a pellet co-culture of the human infrapatellar fat pad (IPFP)-derived mesenchymal stem cells (MSCs) with osteoarthritic chondrocytes increased chondrogenic differentiation [88]. Human IPFP-MSCs seeded on 3D-printed CS scaffolds in chondrogenic media containing TGF-β3 and BMP-6 attach, proliferate, and differentiate into chondrocyte-like cells modulating the formation of cartilaginous tissue in vitro [89].…”

Recent Advance in Source, Property, Differentiation, and Applications of Infrapatellar Fat Pad Adipose-Derived Stem Cells

“…Obese mice have stronger IPFP-ASC adipogenic differentiation potential than thin mice [67]. Hyaluronic acid also can enhance adipogenic differentiation [52]. Lopa et al [84] have reported that IPFP-ASC adipogenic differentiation potential is similar between young people and old people.…”

“…Inducing ASCs after inhibiting ET receptor Promoting adipogenic differentiation [50] 2018 Human Sc-ASCs AtECM Promoting adipogenic differentiation in the first 7 days of differentiation induction [70] 2017 Human IPFP-ASCs Hyaluronic acid Promoting adipogenic differentiation [52] 2017 Human IPFP-ASCs RHEB overexpression in IPFP-ASCs Promoting adipogenic differentiation [56] 2017 Human Sc-ASCs Addition of 2, 5, and 10 μm of pyrintegin Lipid accumulation is the most marked in 2 μm of pyrintegin [85] 2016 Human Sc-ASCs miRNA-29b overexpression in Sc-ASCs Promoting adipogenic differentiation [86] 2016 Human ASCs from Life Technology (USA)…”

Asiatic acid attenuates hypertrophic and fibrotic differentiation of articular chondrocytes via AMPK/PI3K/AKT signaling pathway

“…Cartilage samples were obtained intraoperatively from patients (n = 3, age 55 ± 10) undergoing total knee arthroplasties with approval from Ethics Committee of Southwest Hospital (Chongqing, China). Chondrocytes were isolated according to our previous protocol [19]. Briefly, cartilage pieces were digested in high-glucose DMEM (C11995500BT, Gibco, USA) supplemented with 0.2% type II collagenase (C6885, Sigma, USA) and 1% penicillin/streptomycin (P/S) overnight at 37 °C.…”