Biology subjects

El Haj, A.

Publications and source records attributed to El Haj, A..

3 recordsLinked to original sources

bioRxiv2025

Engineering Extracellular Vesicle Production through Magnetic Ion Channel Activation for Bone Regeneration

Bone disorders represent a significant global health challenge. Extracellular vesicles (EVs) are emerging as a promising nanotherapeutic approach for bone regeneration, addressing the translation barriers associated with cell-based therapies. Despite their immense potential, the clinical application of EVs is limited by low production yields and inconsistent quality. Magnetic Ion Channel Activation (MICA) utilises remote magnetic fields to stimulate mechano-sensitive ion channels through magnetic nanoparticles (MNPs). This study explores the potential of utilising MICA to enhance the production yield and therapeutic efficacy of EVs for bone regeneration. The findings demonstrate that MICA significantly increased the production yield of EVs from MC3T3 pre-osteoblasts compared to magnetic stimulation or TREK1 functionalised graphene oxide-MNP particles alone. The obtained EVs exhibited typical size distribution, morphology, and EV protein expression consistent with nano-sized vesicles. Furthermore, MICA/TREK EVs treatment considerably enhanced human bone marrow-derived mesenchymal stem cells osteogenic differentiation and mineralisation compared to EVs derived from MICA, TREK, or untreated groups. Proteomics analysis revealed the enrichment of proteins involved in mechanotransduction and osteogenic differentiation within MICA/TREK EVs. In summary, these findings highlight the substantial potential of MICA as a platform to enhance the scalable production and therapeutic application of pro-regenerative EVs for bone augmentation strategies.

bioengineering↗

bioRxiv2024

Remote force modulation of the T-cell receptor reveals an NFAT-threshold for CD4+ T cell activation

Abstract/SummaryMechano-modulation of cell surface proteins to influence cell activation has been shown as a promising new advanced therapy for regenerative medicine applications. These strategies rely on the manipulation of mechanosensitive cell surface receptors to initiate intracellular signal transduction. The cell surface receptor of T lymphocytes (TCR), which recognises peptide-MHC molecules central to driving the adaptive immune response, has recently been suggested to be mechano-responsive. Despite this advance, little is known as to whether the TCR can be mechanically modulated to achieve TCR signalling and subsequent T cell activation, and whether these characteristics can be exploited for immunotherapies. Here, we describe a magnetic particle-based platform for mechanical modulation of the TCR and outline how this platform can be utilised to achieve CD4+ T cell activation. We demonstrate that mechanical manipulation of the TCR induces cell surface clustering of the TCR and downstream TCR signalling, leading to eventual TCR downregulation and T cell activation. We investigate the temporal relationship between mechanical modulation of the TCR and subsequent T cell activation, hereby identifying that accumulation of signalling events within the NFAT-pathway is required to reach the threshold required for CD4+ T cell activation, outlining an axis which controls the CD4+ T cell response to external mechanical cues. These findings identify how CD4+ T cells can modulate their function in response to such cues, whilst also outlining a remote-magnetic particle-based platform that may be used for the control of T cell responses.

immunology↗

bioRxiv2020

Parallelized manipulation of adherent living cells by magnetic nanoparticles-mediated forces

The remote actuation of cellular processes such as migration or neuronal outgrowth is a challenge for future therapeutic applications in regenerative medicine. Among the different methods that have been proposed, the use of magnetic nanoparticles appears to be promising since magnetic fields can act at a distance without interactions with the surrounding biological system. To control biological processes at a subcellular spatial resolution, magnetic nanoparticles can be used either to induce biochemical reactions locally or to apply forces on different elements of the cell. Here, we show that cell migration and neurite outgrowth can be directed by the forces produced by a switchable parallelized array of micro-magnetic pillars, following passive uptake of nanoparticles. Using live cell imaging, we first demonstrate that adherent cell migration can be biased toward magnetic pillars and that cells can be reversibly trapped onto these pillars. Second, using differentiated neuronal cells we were able to induce events of neurite outgrowth in the direction of the pillars without impending cell viability. Our results show that the range of forces applied needs to be adapted precisely to the cellular process under consideration. We propose that cellular actuation is the result of the force on the plasma membrane caused by magnetically filled endo-compartments, which exert a pulling force on the cell periphery.

bioengineering↗