Modeling chemotherapy-induced peripheral neuropathy using a Nerve-on-a-chip microphysiological system

Abstract

CIPN), which is rapidly induced after the administration of anti-cancer drugs (Argyriou et al., 2012; Cavaletti and Marmiroli, 2010). Patients with CIPN may experience a range of sensory symptoms including spontaneous tingling, burning pain, and joint and muscle pain in the distal extremities in a "glove and stocking" distribution (Peters et al., 2007). Often, these side effects discourage patient use of the drug, leading to delays or limited dosages and even discontinued treatment altogether (Staff et al., 2017). In some patients, these symptoms resolve following discontinuation of therapy, but an estimated 30% of patients are left with permanent symptoms that affect their overall quality of life (Rivera and Cianfrocca, 2015). Drugs with neurotoxic side effects reaching market approval is attributed to a lack of reliable screens for drug candidate neurotoxicity.Traditional methods for studying neuronal damage and screening neurotoxicity have largely relied on cell and animal models

Systems Pharmacology Modeling Identifies a Novel Treatment Strategy for Bortezomib-Induced Neuropathic Pain

“…Compounds showing promise in animal experimental models of peripheral neuropathy may also fail in clinical settings. The nerve-on-a-chip model in this study utilized rat cells, and further development of microphysiological systems using human primary or iPSC-derived neurons might provide additional insights into species differences in outcomes ( Kramer et al, 2020 ). Lastly, further research is needed to test and verify the mechanisms by which dexanabinol elicits its effects on CIPN in vivo and whether these preclinical results will ultimately translate to human therapeutics.…”

Lab-on-Chip Microsystems for Ex Vivo Network of Neurons Studies: A Review

“…Kramer et al fabricated a lollipop-shaped container using dual hydrogels to develop a myelinated peripheral nerve model, as shown in Figure 5A ( Khoshakhlagh et al, 2018 ; Kramer et al, 2020 ). Neural cells and gliocytes are co-cultured in a spheroid microplate to form a cell sphere that will be moved to the circle part of the container.…”

Advances in 3D neuronal microphysiological systems: towards a functional nervous system on a chip

“…These long-term culture conditions allow for extensive neurite outgrowth in all dimensions with growth-restrictive hydrogels being able to confine dense axon beds to specific areas for electrophysiological recordings. These constructs can then be used for electrophysiological assessment and exhibit peaks that are able to be defined by treatment with drugs (Kramer et al 2020). Additional to neuron function, glia are able to grow and myelinate, more on that next.…”

“…and 3D bioprinted substrates (Antill-O'Brien et al 2019) in order to recreate aspects of 3D macrostructure or neural connectivity seen in the brain. The peripheral nerve has also seen advancements in growing explant or spheroid cultures within anisotropic materials(Anderson et al 2018;George et al 2019) and growth restrictive hydrogels(Huval et al 2015;Nguyen et al 2019;Sharma et al 2019;Kramer et al 2020), respectively. Ultimately, the inherent qualities of anatomical histoarchitecture should guide the design of microarchitectural features of microphysiological devices.…”