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Pancreatic cancer (PC) is a fatal malignancy in the human abdominal cavity that prefers to invade the surrounding nerve/nerve plexus and even the spine, causing devastating and unbearable pain. The limitation of available in vitro models restricts revealing the molecular mechanism of pain and screening pain-relieving strategies to improve the quality of life of end-stage PC patients. Here, we report a PC nerve invasion model that merged human brain organoids (hBrO) with mouse PC organoids (mPCO). After merging hBrOs with mPCOs, we monitored the structural crosstalk, growth patterns, and mutual interaction dynamics of hBrO with mPCOs for 7 days. After 7 days, we also analyzed the pathophysiological statuses, including proliferation, apoptosis and inflammation. The results showed that mPCOs tend to approximate and intrude into the hBrOs, merge entirely into the hBrOs, and induce the retraction/shrinking of neuronal projections that protrude from the margin of the hBrOs. The approximating of mPCOs to hBrOs accelerated the proliferation of neuronal progenitor cells, intensified the apoptosis of neurons in the hBrOs, and increased the expression of inflammatory molecules in hBrOs, including NLRP3, IL-8, and IL-1β. Our system pathophysiologically replicated the nerve invasions in mouse GEMM (genetically engineered mouse model) primary and human PCs and might have the potential to be applied to reveal the molecular mechanism of nerve invasion and screen therapeutic strategies in PCs. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has aggravated a preexisting epidemic: the opioid crisis. Much literature has shown that the circumstances imposed by COVID-19, such as social distancing regulations, medical and financial instability, and increased mental health issues, have been detrimental to those with opioid use disorder (OUD). In addition, unexpected neurological sequelae in COVID-19 patients suggest that COVID-19 compromises neuroimmunity, induces hypoxia, and causes respiratory depression, provoking similar effects as those caused by opioid exposure. Combined conditions of COVID-19 and OUD could lead to exacerbated complications. With limited human in vivo options to study these complications, we suggest that iPSC-derived brain organoid models may serve as a useful platform to investigate the physiological connection between COVID-19 and OUD. This mini-review highlights the advances of brain organoids in other neuropsychiatric and infectious diseases and suggests their potential utility for investigating OUD and COVID-19, respectively. [ABSTRACT FROM AUTHOR]