Investigating neuro-immune interaction in a humanised in vitro microfluidic coculture platform
Chang P-S., Song S., DAVIES A., SCHMID A.
Neuropathic pain is a devastating condition affecting 9% of the population worldwide. Among the most common causes are entrapment neuropathies and focal nerve injuries. The inadequacy of treatments stems in part from a lack of understanding regarding the pathophysiology of neuropathic pain and limited translation from preclinical murine models to humans. My research combines human tissues with humanised models to decipher the underlying mechanisms of neuropathic pain for drug development. Neuroinflammation is a main driver of neuropathic pain. Through bulk RNA sequencing and histological staining of human nerve, I have identified a pain-associated glucocorticoid-induced macrophage subtype (MGC; CD163+STAB1+MARCO+), in the painful entrapment neuropathy - Morton’s neuroma. To interrogate its role in human neuropathic pain, I have established an in vitro microfluidic platform to coculture MGC-like macrophages (CD163+STAB1+MARCOdim) with human induced pluripotent stem cell-derived sensory neurons (hiPSCdSN). I use GCaMP-based live cell calcium imaging and a 'Fast Fourier Transform'-based analysis pipeline to investigate the effect of MGC-like macrophages on the spontaneous activity of injured or healthy hiPSCdSN. My first experiment identifies MGC-like macrophages enhance the level of spontaneous activity in hiPSCdSN 4 days after in vitro axonal injury at the neurite side compared to M0 macrophages.