Bessy, T. | bioRxiv Science

bioRxiv2025

The NaaS Methodology applied to modeling chemotherapy-induced peripheral neuropathy with human hiPSC neurons

The Neuron-as-a-Sensor (NaaS) methodology is a human-relevant platform designed to detect compound-induced effects by capturing functional changes in neuronal activity. This is achieved by integrating hiPSC-derived neuronal cultures, compartmentalized MEA microfluidic devices, a detailed electrophysiology paradigm and a standardized analysis pipeline. Applied to chemotherapy-induced peripheral neuropathy (CIPN), NaaS leverages electrophysiological profiling to capture alterations in neuronal excitability beyond cytotoxicity. Using paclitaxel and oxaliplatin as reference compounds, we demonstrated drug-specific, time-dependent changes in spontaneous and thermally evoked activity that align with their distinct clinical neuropathic phenotypes. Dimensionality reduction of electrophysiological metrics enabled construction of a functional discrimination map, allowing robust separation of compound signatures from vehicle controls. These findings highlight the ability of NaaS to model clinically relevant neurotoxic effects in a scalable manner, supporting its application in both adverse effect prediction and therapeutic screening.

bioengineering↗

bioRxiv2020

Hematopoietic progenitors polarize in contact with bone marrow stromal cells by engaging CXCR4 receptors.

Hematopoietic stem and progenitor cells (HSPCs) are located in the bone marrow, where they regulate the permanent production and renewal of all blood-cell types. HSPC proliferation and differentiation is locally regulated by their interaction with cells forming specific microenvironments close to the bone matrix or close to blood vessels. However, the cellular mechanisms underlying HSPCs interaction with these cells and their potential impact on HSPC polarity is still poorly understood. Here we modelled the bone-marrow niche using microfluidic technologies in a bone-marrow on a chip device, and evaluated long-duration cell-cell contacts between single HSPCs and stromal cells or endothelial cells in a custom-designed microwell cell-culture system. We found that an HSPC can form a discrete contact site that leads to the extensive polarization of their cytoskeleton architectures. As in the case with immune synapses formed by lymphocytes, the centrosome was located in proximity of the cell-cell contact. The entire microtubule network emanated from the centrosome, and the nucleus was confined to the side opposite of the cell-cell contact. The capacity of the HSPC to polarize appeared specific as it was not observed in contact with skin fibroblasts. The receptors ICAM, VCAM and CXCR4 were identified in the polarizing contact, and were all independently capable of inducing morphological polarization. However, only CXCR4 was independently capable of inducing the polarization of the centrosome-microtubule network. Altogether these results revealed a novel mechanism of HSPC polarization associated with its anchorage to specific cells in the bone-marrow, which might be instrumental in the regulation of their fate.

cell biology↗