Engineering human spinal microphysiological systems to model opioid-induced tolerance

Cai, Hongwei; Ao, Zheng; Tian, Chunhui; Wu, Zhuhao; Kaurich, Connor; Chen, Zi; Gu, Mingxia; Hohmann, Andrea G.; Guo, Feng

doi:10.1016/j.bioactmat.2022.10.007

Cited by 14 publications

(8 citation statements)

References 59 publications

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“…The use of organoids in vitro for physiological modeling and disease representation has achieved breakthroughs in several fields. These include early neural system development, trunk formation, visual pathway projections, nociceptive sensory circuits, signal transmission from brain to spinal cord, human nociceptive perception and opioid-induced tolerance, neuromuscular junctions, leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL), neural tube defects (NTDs), amyotrophic lateral sclerosis (ALS), acute flaccid myelitis (AFM), and glaucoma. − In summary, spinal cord organoids induced by DBECMH and small molecules offer an innovative, mass-amplifiable, and individually specific in vitro spinal cord model. This lays the groundwork for using organoids to construct in vitro models of spinal cord diseases, significantly advancing the field of medical research and therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization

Wu,

Liu,

Liu

et al. 2024

ACS Biomater. Sci. Eng.

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The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.

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Section: Discussionmentioning

confidence: 99%

Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization

Wu,

Liu,

Liu

et al. 2024

ACS Biomater. Sci. Eng.

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“…Furthermore, studies of opioid activity and dynamics may also be expanded to include CNS components outside of the brain. This may be done through bioengineered platforms for organoid generation, such as those recapitulating the spinal cord and blood–brain barrier ( Brown et al, 2020 ; Cai et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Investigating the neurobiology of maternal opioid use disorder and prenatal opioid exposure using brain organoid technology

Dwivedi,

Haddad

2024

Front. Cell. Neurosci.

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Over the past two decades, Opioid Use Disorder (OUD) among pregnant women has become a major global public health concern. OUD has been characterized as a problematic pattern of opioid use despite adverse physical, psychological, behavioral, and or social consequences. Due to the relapsing–remitting nature of this disorder, pregnant mothers are chronically exposed to exogenous opioids, resulting in adverse neurological and neuropsychiatric outcomes. Collateral fetal exposure to opioids also precipitates severe neurodevelopmental and neurocognitive sequelae. At present, much of what is known regarding the neurobiological consequences of OUD and prenatal opioid exposure (POE) has been derived from preclinical studies in animal models and postnatal or postmortem investigations in humans. However, species-specific differences in brain development, variations in subject age/health/background, and disparities in sample collection or storage have complicated the interpretation of findings produced by these explorations. The ethical or logistical inaccessibility of human fetal brain tissue has also limited direct examinations of prenatal drug effects. To circumvent these confounding factors, recent groups have begun employing induced pluripotent stem cell (iPSC)-derived brain organoid technology, which provides access to key aspects of cellular and molecular brain development, structure, and function in vitro. In this review, we endeavor to encapsulate the advancements in brain organoid culture that have enabled scientists to model and dissect the neural underpinnings and effects of OUD and POE. We hope not only to emphasize the utility of brain organoids for investigating these conditions, but also to highlight opportunities for further technical and conceptual progress. Although the application of brain organoids to this critical field of research is still in its nascent stages, understanding the neurobiology of OUD and POE via this modality will provide critical insights for improving maternal and fetal outcomes.

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“…27 In addition, flattened organoids were developed to provide adequate nutrient and oxygen supply, which helps prevent conditions such as hypoxia and necrosis. 28 The flattened organoids also ensure a consistent exposure to inducing factors throughout the development of organoids, resulting in a more uniform differentiation process and the formation of homogeneous tissue. To overcome the diffusion limit and develop cortical organoids that closely resemble the late-stage human cortex, the sliced neocortical organoid (SNO) system was introduced.…”

Section: Technical Advancements In Developing Mpsmentioning

confidence: 99%

Progress in developing microphysiological systems for biological product assessment

Mansouri,

Lam,

Sung

2024

Lab Chip

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Engineering human spinal microphysiological systems to model opioid-induced tolerance

Cited by 14 publications

References 59 publications

Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization

Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization

Investigating the neurobiology of maternal opioid use disorder and prenatal opioid exposure using brain organoid technology

Progress in developing microphysiological systems for biological product assessment

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