The application of induced pluripotent stem cells (iPSCs) in disease modeling and regenerative medicine can be limited by the prolonged times required for functional human neuronal differentiation and traditional 2D culture techniques. Here, a conductive graphene scaffold (CGS) to modulate mechanical and electrical signals to promote human iPSC-derived neurons is presented. The soft CGS with cortex-like stiffness (≈3 kPa) and electrical stimulation (±800 mV/100 Hz for 1 h) incurs a fivefold improvement in the rate (14d) of generating iPSC-derived neurons over some traditional protocols, with an increase in mature cellular markers and electrophysiological characteristics. Consistent with other culture conditions, it is found that the pro-neurogenic effects of mechanical and electrical stimuli rely on RhoA/ROCK signaling and de novo ciliary neurotrophic factor (CNTF) production respectively. Thus, the CGS system creates a combined physical and continuously modifiable, electrical niche to efficiently and quickly generate iPSC-derived neurons.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025039 | PMC |
http://dx.doi.org/10.1002/advs.202002112 | DOI Listing |
Sci Rep
December 2024
Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore.
Signaling interplay between the histamine 1 receptor (H1R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) in mediating histaminergic itch has been well-established in mammalian models, but whether this is conserved in humans remains to be confirmed due to the difficulties in obtaining human sensory neurons (SNs) for experimentation. Additionally, previously reported species-specific differences in TRPV1 function indicate that use of human SNs is vital for drug candidate screening to have a higher chance of identifying clinically effective TRPV1 antagonists. In this study, we built a histamine-dependent itch model using peripheral SNs derived from human induced pluripotent stem cells (hiPSC-SNs), which provides an accessible source of human SNs for pre-clinical drug screening.
View Article and Find Full Text PDFFEBS J
December 2024
Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, UK.
The microglial triggering receptor expressed on myeloid cells 2 (TREM2) is required for diverse microglia responses in neurodegeneration, including immunometabolic plasticity, phagocytosis, and survival. We previously identified that patient iPSC-derived microglia (iPS-Mg) harboring the Alzheimer's disease (AD) TREM2 hypomorph display several functional deficits linked to metabolism. To investigate whether these deficits are associated with disruptions in metabolite signaling, we generated common variant, TREM2 and TREM2 variant human iPS-Mg.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, Milan, Italy.
The development of ground-breaking Survival Motor Neuron (SMN) replacement strategies has revolutionized the field of Spinal Muscular Atrophy (SMA) research. However, the limitations of these therapies have now become evident, highlighting the need for the development of complementary targets beyond SMN replacement. To address these challenges, here we explored, in in vitro and in vivo disease models, Stathmin-2 (STMN2), a neuronal microtubule regulator implicated in neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), as a novel SMN-independent target for SMA therapy.
View Article and Find Full Text PDFMol Ther Nucleic Acids
December 2024
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA.
There is an urgent need for agents that promote health and regeneration of cells and tissues, specifically to treat diseases of the aging nervous system. Age-associated nervous system degeneration and various diseases are driven by many different biochemical stresses, often making it difficult to target any one disease cause. Our laboratory has previously identified DNA aptamers with apparent regenerative properties in murine models of multiple sclerosis by selecting aptamers that bind oligodendrocyte membrane preparations.
View Article and Find Full Text PDFJ Cell Biol
February 2025
Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Endocytosis, required for the uptake of receptors and their ligands, can also introduce pathological aggregates such as α-synuclein (α-syn) in Parkinson's Disease. We show here the unexpected presence of intrinsically perforated endolysosomes in neurons, suggesting involvement in the genesis of toxic α-syn aggregates induced by internalized preformed fibrils (PFFs). Aggregation of endogenous α-syn in late endosomes and lysosomes of human iPSC-derived neurons (iNs), seeded by internalized α-syn PFFs, caused the death of the iNs but not of the parental iPSCs and non-neuronal cells.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!