Neural patterning of human induced pluripotent stem cells for studying neurotoxicity

Existing models using adult human neural stem cells have the restricted access. Human induced pluripotent stem cells (hiPSCs) can generate allogeneic or patient-specific neural cells/tissues and even mini-brains to provide robust in vitro models for applications in drug discovery, neurological disease modeling, and cell therapy. Toward this goal, the objective of this study is to construct 3-D neural models from hiPSCs through the scalable embryoid body-based suspension culture which can generate cortical glutamatergic neurons and motor neurons by tuning the sonic hedgehog (SHH) signaling. The differentiation of human iPSK3 cells was induced using dual inhibition of SMAD signaling with LDN193189 and SB431542. Then the neural tissue patterning was tuned through the treatment with cyclopamine (the SHH antagonist) or purmorphamine (the SHH agonist) along with other factors and further maturation. The neural cells were characterized at day 20, day 35, and day 55. Abundant glutamatergic neurons (\u3e60%) was observed with the cyclopamine treatment, while the cells were more enriched with motor neurons expressing Islet-1 and HB9 (\u3e40%) with the purmorphamine treatment. The cells also expressed pre- and post-synaptic markers (Synapsin I and PSD95), and generated action potentials in response to depolarizing current injections and spontaneous excitatory post-synaptic currents after maturation. To assess the cellular responses, three classes of small molecules/drugs were investigated: (1) N-methyl-D-aspartate to induce general neural toxicity; (2) matrix metalloproteinases inhibitors to affect matrix remodeling; (3) amyloid β (1-42) oligomers to induce disease-specific neural toxicity. Differential responses to various treatments were observed for different neuronal subtypes. Overall, this study can provide a transformative approach to establish 3-D neural models for neurological disease modeling (e.g., Alzheimer’s disease), drug discovery, and cell therapy

Downlink and Uplink Intelligent Reflecting Surface Aided Networks: NOMA and OMA

Intelligent reflecting surfaces (IRSs) are envisioned to provide reconfigurable wireless environments for future communication networks. In this paper, both downlink and uplink IRS-aided non-orthogonal multiple access (NOMA) and orthogonal multiple access (OMA) networks are studied, in which an IRS is deployed to enhance the coverage by assisting a cell-edge user device (UD) to communicate with the base station (BS). To characterize system performance, new channel statistics of the BS-IRS-UD link with Nakagami-$m$ fading are investigated. For each scenario, the closed-form expressions for the outage probability and ergodic rate are derived. To gain further insight, the diversity order and high signal-to-noise ratio (SNR) slope for each scenario are obtained according to asymptotic approximations in the high-SNR regime. It is demonstrated that the diversity order is affected by the number of IRS reflecting elements and Nakagami fading parameters, but the high-SNR slope is not related to these parameters. Simulation results validate our analysis and reveal the superiority of the IRS over the full-duplex decode-and-forward relay.Comment: Accepted for publication in the IEEE Transactions on Wireless Communication