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Enhanced Chondrogenic Capacity of Mesenchymal Stem Cells After TNF? Pre-treatment.

ABSTRACT: Mesenchymal stem cells (MSCs) are promising cells to treat cartilage defects due to their chondrogenic differentiation potential. However, an inflammatory environment during differentiation, such as the presence of the cytokine TNF?, inhibits chondrogenesis and limits the clinical use of MSCs. On the other hand, it has been reported that exposure to TNF? during in vitro expansion can increase proliferation, migration, and the osteogenic capacity of MSCs and therefore can be beneficial for tissue regeneration. This indicates that the role of TNF? on MSCs may be dependent on the differentiation stage. To improve the chondrogenic capacity of MSCs in the presence of an inflamed environment, we aimed to determine the effect of TNF? on the chondrogenic differentiation capacity of MSCs. Here, we report that TNF? exposure during MSC expansion increased the chondrogenic differentiation capacity regardless of the presence of TNF? during chondrogenesis and that this effect of TNF? during expansion was reversed upon TNF? withdrawal. Interestingly, pre-treatment with another pro-inflammatory cytokine, IL-1?, did not increase the chondrogenic capacity of MSCs indicating that the pro-chondrogenic effect is specific for TNF?. Finally, we show that TNF? pre-treatment increased the levels of SOX11 and active ?-catenin suggesting that these intracellular effectors may be useful targets to improve MSC-based cartilage repair. Overall, these results suggest that TNF? pre-treatment, by modulating SOX11 levels and WNT/?-catenin signaling, could be used as a strategy to improve MSC-based cartilage repair.

SUBMITTER: Voskamp C

PROVIDER: S-EPMC7344141 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Enhanced Chondrogenic Capacity of Mesenchymal Stem Cells After TNFα Pre-treatment.

Voskamp Chantal C Koevoet Wendy J L M WJLM Somoza Rodrigo A RA Caplan Arnold I AI Lefebvre Véronique V van Osch Gerjo J V M GJVM Narcisi Roberto R

Frontiers in bioengineering and biotechnology 20200630

Mesenchymal stem cells (MSCs) are promising cells to treat cartilage defects due to their chondrogenic differentiation potential. However, an inflammatory environment during differentiation, such as the presence of the cytokine TNFα, inhibits chondrogenesis and limits the clinical use of MSCs. On the other hand, it has been reported that exposure to TNFα during <i>in vitro</i> expansion can increase proliferation, migration, and the osteogenic capacity of MSCs and therefore can be beneficial for ...[more]

PMID: 32714905

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Project description:BACKGROUND:Nanosecond pulsed electric fields (nsPEFs) can produce more significant biological effects than traditional electric fields and have thus attracted rising attention in developing medical applications based on short pulse duration and high field strength, such as effective cancer therapy. However, little is known about their effects on the differentiation of stem cells. Furthermore, mechanisms of electric fields on chondrogenic differentiation of mesenchymal stem cells (MSCs) remain elusive, and effects of electric fields on cartilage regeneration need to be verified in vivo. Here, we aimed to study the effects of nsPEFs on chondrogenic differentiation of MSCs in vitro and in vivo and further to explore the mechanisms behind the phenomenon. METHODS:The effects of nsPEF-preconditioning on chondrogenic differentiation of mesenchymal stem cells (MSCs) in vitro were evaluated using cell viability, gene expression, glycosaminoglycan (sGAG) content, and histological staining, as well as in vivo cartilage regeneration in osteochondral defects of rats. Signaling pathways were investigated with protein expression and gene expression, respectively. RESULTS:nsPEF-preconditioning with proper parameters (10?ns at 20?kV/cm, 100?ns at 10?kV/cm) significantly potentiated chondrogenic differentiation capacity of MSCs with upregulated cartilaginous gene expression and increased matrix deposition through activation of C-Jun NH2-terminal kinase (JNK) and cAMP-response element binding protein (CREB), followed by activation of downstream signal transducer and activator of transcription (STAT3). Implantation of nsPEF-preconditioned MSCs significantly enhanced cartilage regeneration in vivo, compared with implantation of non-nsPEF-preconditioned MSCs. CONCLUSION:This study demonstrates a unique approach of nsPEF treatment to potentiate the chondrogenic ability of MSCs through activation of JNK/CREB-STAT3 that could have translational potential for MSC-based cartilage regeneration.

Project description:BackgroundDirect intra-articular injection (DIAI) of mesenchymal stem cells (MSCs) is a promising technique for cartilage repair. However, the repair process was hindered by the absence of scaffold and poor cell-matrix interactions.MethodsIn this study, we developed a pericellular collagen I coating (PCC) on MSCs. The overall performances of MSC-PCC homing, chondrogenic differentiation, and cartilage regeneration have been comprehensively evaluated in a New Zealand rabbit model. Firstly, we examined the morphology and physical characteristics of PCC. Secondly, MSC ex-vivo cartilage slice adhesion and in-vivo cartilage defect homing were observed using multiscale methods. Thirdly, the precartilage condensation of cell pellets formed by aggregation of MSCs was examined to evaluate the cartilage-inducing potential of PCC. Finally, the cartilage regeneration by DIAI of PCC-coated MSCs was observed and scored macroscopically and histologically.ResultsIn general, the cell adhesion and homing assay revealed that PCC facilitated MSC adhesion on cartilage slices, enhancing MSC homing and retention to cartilage defect. This increased homing ratio was accompanied by an increasing cell-cell contact. Compared with naked MSCs, the cell pellets formed by PCC-coated MSCs exhibited more evident appearance of condensation. In pellets, cell-cell interaction has been significantly stimulated, inducing the expression of condensation marker N-cadherin, and subsequent chondrogenic marker collagen II and aggrecan. By 12 weeks after DIAI, cartilage defects have been repaired by MSCs to varying degrees. Overall, PCC significantly enhances the quality of cartilage regeneration judging from macroscopic observation, ICRS score, histological examination, and collagen type I, II, and X immunohistochemical staining.ConclusionsThe capacity and viability of MSCs can be enhanced by collagen I coating, which provides cues for enhancing cell homing and differentiation. Our method provides a novel strategy for stem cell therapy.

Dataset Information

Enhanced Chondrogenic Capacity of Mesenchymal Stem Cells After TNF? Pre-treatment.

Publications

Enhanced Chondrogenic Capacity of Mesenchymal Stem Cells After TNFα Pre-treatment.

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