{"doi":"10.1101/2025.08.31.673344","title":"Human microphysiological model of dorsal root ganglion-spinal cord dorsal horn circuitry recapitulates opioid induced effects","abstract":"Microphysiological systems (MPSs) are engineered, in vitro platforms which have been established as viable alternatives to animal models for pre-clinical research with unique advantages over conventional model systems. Many MPSs utilize 3-dimensional (3D) tissue constructs that enable biomimetic cell-cell interactions, allow for extended culture periods, and provide the time necessary for the emergence of physical and physiological characteristics of more mature tissues. Here, we present a novel MPS using human induced pluripotent stem cell (hiPSC)-derived spinal cord dorsal horn (SCDH) spheroids co-cultured with hiPSC-derived dorsal root ganglion (DRG) sensory spheroids in a microengineered hydrogel system to create a \"connectoid\" model of afferent pain circuitry. SCDH spheroids were functionally innervated by peripheral sensory neurons, and prolonged maturation of hiPSC-derived SCDH neurons within the connectoid system enabled derivation of crucial late-born cell types unattainable using 2D differentiations. Furthermore, hiPSC-derived SCDH spheroids spontaneously generate rhythmic, complex, synaptically-driven electrophysiological waveforms that are disinhibited by morphine exposure, consistent with spinal mechanisms of opioid-induced pruritus and hypersensitivity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558980,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1328502,"name":"Frank Siepel","orcid":"0000-0001-7823-5561","position":1,"is_corresponding":false},{"id":467863,"name":"Nisha Iyer","orcid":"0000-0002-9597-0936","position":2,"is_corresponding":false},{"id":811424,"name":"Alexander Bosak","orcid":"0000-0002-7531-8051","position":3,"is_corresponding":false},{"id":395305,"name":"Randolph S. Ashton","orcid":"0000-0002-6842-7022","position":4,"is_corresponding":false},{"id":724607,"name":"Michael J. Moore","orcid":"0000-0002-7853-5756","position":5,"is_corresponding":false},{"id":724604,"name":"Kevin Pollard","orcid":"0000-0002-8503-0393","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:30.312295Z","pmid":"40950113","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}