1,720,976 research outputs found
Altered lysosomal abundance and activity in Charcot-Marie-Tooth disease type 1A (late breaking abstract)
No full textAltered lysosomal abundance and activity in Charcot-Marie-Tooth disease type 1A (late breaking abstract)
No full textGAP JUNCTIONS: THE HOLY GRAIL IN STEM CELL-BASED SUICIDE GENE THERAPY FOR HEAD AND NECK CANCER
No full textGap junctions: the holy grail in stem cell-based suicide gene therapy for head and neck cancer
No full text
Gap junctions: the holy grail in stem cell-based suicide gene therapy for head and neck cancer
No full textGAP JUNCTIONS: THE HOLY GRAIL IN STEM CELL-BASED SUICIDE GENE THERAPY FOR HEAD AND NECK CANCER
No full text
Human dental pulp stem cells as a patient-in-a-dish model for charcot-Marie-tooth disease type 1A
No full textIntroduction: Charcot-Marie-Tooth disease type 1A (CMT1A) is the most prevalent demyelinating peripheral neuropathy worldwide. CMT1A is caused by the duplication of the peripheral myelin protein 22 (PMP22) gene, predominantly affecting Schwann cells. Many CMT1A candidate drugs have failed trials due to a lack of clinically relevant in vitro models. Remarkably, human Dental Pulp Stem Cells (DPSC), a subset of mesenchymal stem cells, share their embryonic lineage with Schwann cells: the neural crest. Our research group has pioneered a differentiation protocol to generate DPSC-derived Schwann cells (DPSC-SC). Hence, we aim to develop a novel CMT1A patient-in-a-dish model by overexpressing PMP22 in DPSC-SC. Methods: Ten healthy DPSC donor lines were isolated from third molars using the explant method. Following differentiation towards DPSC-SC, Schwann cell phenotype was determined using qPCR and immunocytochemistry. Additionally, DPSC-SC myelination capacity was further evaluated in a 3D hydrogel co-culture model with rat dor-sal root ganglion neurons. Finally, lentiviral transduction and CRISPR-Cas9 were used to overexpress PMP22. Results: Ten donor DPSC-SC lines displayed relatively stable gene and protein expression of P75NTR, S100B, SOX10, and laminin, validating the consistency of the differentiation. Our data revealed variable expression patterns of myelin-related genes (MPZ, PLP1, KROX20, OCT6, SOX2, C-JUN, and NCAM). However, DPSC-SC successfully myelinated rat neurons in a 3D hydrogel model, highlighting the importance of neuronal interactions. Moreover, we overexpressed PMP22 in DPSC and DPSC-SC using lentiviral transduction and successfully integrated one additional copy of PMP22 in DPSC using CRISPR-Cas9. Conclusions: We successfully differentiated ten donor DPSC lines towards a Schwann cell phenotype that were able to myelinate rat neurons in a hydrogel model. Moreover, we successfully overex-pressed PMP22 in DPSC-SC and DPSC using lentiviral transduction and CRISPR-Cas9, respectively. These PMP22-overexpressing DPSC-SC offer a novel toolbox for studying CMT1A and PMP22-related mechanisms with high clinical relevance.FWO Flander
Investigating ferroptosis and altered antioxidant signaling in Charcot-Marie-Tooth disease typy 1A
No full textaddition, we confirmed a significant reduction in the expression of GDAP1 within patient-derived cells, providing a direct link to disease pathology. Our preliminary functional assessments revealed that GDAP1 mutation had a discernible impact within the spheroid model. Conclusions: Overall, our study highlights the importance of developing physiologically relevant models for a deeper understanding of CMT and the pursuit of effective treatments. Building on these findings , our future endeavors will aim to further enhance the complexity of our model system by establishing an all-human in vitro neuromus-cular junction in a customized microfluidic chip.FWO PhD Fellowship fundamental research (Belgium
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