ArticleAdvanced biology2024
Human IPSC-Derived PreBötC-Like Neurons and Development of an Opiate Overdose and Recovery Model.
Article in Advanced biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 3 citations in OpenAlex.
- Stem Cell Models for Elucidating Cellular Mechanisms of Substance Use Disorders and Advancing Addiction Pharmacology.Stem cells international · 2026Review
- Nonclinical human neural new approach methodologies (NAMs): Electrophysiological assessment of opioid agonist and antagonist combination.NAM journal · 2025Article
- Microphysiological system to address the opioid crisis: A novel multi-organ model of acute opioid overdose and recovery.Current research in toxicology · 2025Article
- Investigating the neurobiology of maternal opioid use disorder and prenatal opioid exposure using brain organoid technology.Frontiers in cellular neuroscience · 2024Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Opioid overdose is the leading cause of drug overdose lethality, posing an urgent need for investigation. The key brain region for inspiratory rhythm regulation and opioid-induced respiratory depression (OIRD) is the preBötzinger Complex (preBötC) and current knowledge has mainly been obtained from animal systems. This study aims to establish a protocol to generate human preBötC neurons from induced pluripotent cells (iPSCs) and develop an opioid overdose and recovery model utilizing these iPSC-preBötC neurons. A de novo protocol to differentiate preBötC-like neurons from human iPSCs is established. These neurons express essential preBötC markers analyzed by immunocytochemistry and demonstrate expected electrophysiological responses to preBötC modulators analyzed by patch clamp electrophysiology. The correlation of the specific biomarkers and function analysis strongly suggests a preBötC-like phenotype. Moreover, the dose-dependent inhibition of these neurons' activity is demonstrated for four different opioids with identified IC50's comparable to the literature. Inhibition is rescued by naloxone in a concentration-dependent manner. This iPSC-preBötC mimic is crucial for investigating OIRD and combating the overdose crisis and a first step for the integration of a functional overdose model into microphysiological systems.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.