Nano-Ghosts: Mesenchymal Stem Cells Derived Nanoparticles as a Novel Approach for Cartilage Regeneration

Domenico D'Atri 1 Joao Garcia 2 Laura Creemers 2 Marcelle Machluf 1
1Technion Israel Institute of Technology, Israel
2University Medical Center Utrecht, The Netherlands

Background: Osteoarthritis is a joints’ inflammatory disease which is characterized by cartilage degeneration. Mesenchymal stem cells (MSCs) play an essential role in inflammation, due to their homing and modulatory characteristics. We designed innovative nanoparticles termed Nano-Ghosts (NGs), derived from the cytoplasmic membrane of the MSCs. Retaining MSCs’ surface properties, NGs are expected to target and modulate inflamed tissue. In this study, we demonstrate NGs’ ability to target articular chondrocytes (hACs) and cartilage explants while reducing inflammation.

Methods: Targeting was evaluated by flow cytometry and confocal microscopy. NGs’ anti-inflammatory properties were studied in vitro on TNFa-stimulated and naïve hACs and, ex vivo, on cartilage explants. qPCR and ELISA of various markers assessed anti-inflammatory effect.

Results: Flow cytometry showed that NGs target in vitro both TNFa-stimulated and naïve hACs with 4 times higher efficiency towards inflamed cells. Targeting was confirmed by confocal microscopy and imaging flow cytometry which showed that NGs bound the membrane and penetrated the cells. Similarly, in human explants, the particles showed 4 times higher binding to TNFa-stimulated explants. Different anti-inflammatory markers such as NO2, IL6, PGE2 and MMP13 were analyzed. Our data showed that NGs reduce inflammation by more than 50% at the protein and RNA level.

Conclusions: Here we show a proof-of-concept NGs with intrinsic targeting capabilities for targeted cartilage regeneration. NGs may represent a novel strategy for treatment of OA as an anti-inflammatory carrier for targeted delivery of therapeutics, such as growth factors. Ongoing in vivo studies are focused on targeting mechanisms and anti-inflammatory properties.

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