Human Brain Organoid Platform for Neuroengineering Optical Theranostics in Neonatal Sepsis

2021 ◽  
pp. 753-757
Author(s):  
Sneha S. Karanth ◽  
Radhika Mujumdar ◽  
Jagdish P. Sahoo ◽  
Abhijit Das ◽  
Michal K. Stachowiak ◽  
...  
Keyword(s):  
Human Brain ◽  
Neonatal Sepsis ◽  
Brain Organoid

scholarly journals Immune Factor, TNFα, Disrupts Human Brain Organoid Development Similar to Schizophrenia—Schizophrenia Increases Developmental Vulnerability to TNFα

2020 ◽  
Vol 14 ◽  
Author(s):  
Courtney A. Benson ◽  
Hana R. Powell ◽  
Michal Liput ◽  
Siddhartha Dinham ◽  
David A. Freedman ◽  
...  
Keyword(s):  
Human Brain ◽  
Immune Factor ◽  
Brain Organoid

scholarly journals Complex Activity and Short-term Memories in Reciprocally Connected Cerebral Organoids

2021 ◽  
Author(s):  
Tatsuya Osaki ◽  
Yoshiho Ikeuchi
Keyword(s):  
Human Brain ◽  
Three Dimensional ◽  
Oscillatory Activity ◽  
Cellular Functions ◽  
Complex Activity ◽  
Axonal Connections ◽  
Brain Organoid ◽  
External Stimuli ◽  
The Brain

AbstractMacroscopic axonal connections in the human brain distribute information and neuronal activity across the brain. Although this complexity previously hindered elucidation of functional connectivity mechanisms, brain organoid technologies have recently provided novel avenues to investigate human brain function by constructing small segments of the brain in vitro. Here, we describe the neural activity of human cerebral organoids reciprocally connected by a bundle of axons. Compared to conventional organoids, connected organoids produced significantly more intense and complex oscillatory activity. Optogenetic manipulations revealed that the connected organoids could re-play and recapitulate over time temporal patterns found in external stimuli, indicating that the connected organoids were able to form and retain temporal memories. Our findings suggest that connected organoids may serve as powerful tools for investigating the roles of macroscopic circuits in the human brain – allowing researchers to dissect cellular functions in three-dimensional in vitro nervous system models in unprecedented ways.

scholarly journals Moral Limits of Brain Organoid Research

2019 ◽  
Vol 47 (4) ◽  
pp. 760-767 ◽  
Author(s):  
Julian J. Koplin ◽  
Julian Savulescu
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Stem Cell Research ◽  
Cognitive Abilities ◽  
Moral Status ◽  
Ethical Challenges ◽  
Ethical Concerns ◽  
Moral Framework ◽  
Brain Organoid ◽  
Regulations And Guidelines

Brain organoid research raises ethical challenges not seen in other forms of stem cell research. Given that brain organoids partially recapitulate the development of the human brain, it is plausible that brain organoids could one day attain consciousness and perhaps even higher cognitive abilities. Brain organoid research therefore raises difficult questions about these organoids' moral status – questions that currently fall outside the scope of existing regulations and guidelines. This paper shows how these gaps can be addressed. We outline a moral framework for brain organoid research that can address the relevant ethical concerns without unduly impeding this important area of research.

scholarly journals Challenges in Modeling Human Neural Circuit Formation via Brain Organoid Technology

2020 ◽  
Vol 14 ◽  
Author(s):  
Takeshi K. Matsui ◽  
Yuichiro Tsuru ◽  
Ken-ichiro Kuwako
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Neural Circuit ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Neural Lineage ◽  
Human Brain Development ◽  
Brain Organoid ◽  
Circuit Formation

Human brain organoids are three-dimensional self-organizing tissues induced from pluripotent cells that recapitulate some aspects of early development and some of the early structure of the human brain in vitro. Brain organoids consist of neural lineage cells, such as neural stem/precursor cells, neurons, astrocytes and oligodendrocytes. Additionally, brain organoids contain fluid-filled ventricle-like structures surrounded by a ventricular/subventricular (VZ/SVZ) zone-like layer of neural stem cells (NSCs). These NSCs give rise to neurons, which form multiple outer layers. Since these structures resemble some aspects of structural arrangements in the developing human brain, organoid technology has attracted great interest in the research fields of human brain development and disease modeling. Developmental brain disorders have been intensely studied through the use of human brain organoids. Relatively early steps in human brain development, such as differentiation and migration, have also been studied. However, research on neural circuit formation with brain organoids has just recently began. In this review, we summarize the current challenges in studying neural circuit formation with organoids and discuss future perspectives.

Human brain organoid-on-a-chip to model prenatal nicotine exposure

Lab on a Chip ◽  
2018 ◽  
Vol 18 (6) ◽  
pp. 851-860 ◽  
Author(s):  
Yaqing Wang ◽  
Li Wang ◽  
Yujuan Zhu ◽  
Jianhua Qin
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Nicotine Exposure ◽  
Prenatal Nicotine Exposure ◽  
New Strategy ◽  
Organ On A Chip ◽  
Prenatal Nicotine ◽  
Brain Organoid

We present a new strategy to generate stem cell based human brain organoids using an organ-on-a-chip system that allows us to model prenatal nicotine exposure.

scholarly journals Unraveling Human Brain Development and Evolution Using Organoid Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Sarah Fernandes ◽  
Davis Klein ◽  
Maria C. Marchetto
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Brain Region ◽  
Model Systems ◽  
Transcriptional Signature ◽  
Human Brain Development ◽  
Advanced Stages ◽  
Brain Organoid ◽  
Development And Evolution ◽  
Human Specific

Brain organoids are proving to be physiologically relevant models for studying human brain development in terms of temporal transcriptional signature recapitulation, dynamic cytoarchitectural development, and functional electrophysiological maturation. Several studies have employed brain organoid technologies to elucidate human-specific processes of brain development, gene expression, and cellular maturation by comparing human-derived brain organoids to those of non-human primates (NHPs). Brain organoids have been established from a variety of NHP pluripotent stem cell (PSC) lines and many protocols are now available for generating brain organoids capable of reproducibly representing specific brain region identities. Innumerous combinations of brain region specific organoids derived from different human and NHP PSCs, with CRISPR-Cas9 gene editing techniques and strategies to promote advanced stages of maturation, will successfully establish complex brain model systems for the accurate representation and elucidation of human brain development. Identified human-specific processes of brain development are likely vulnerable to dysregulation and could result in the identification of therapeutic targets or disease prevention strategies. Here, we discuss the potential of brain organoids to successfully model human-specific processes of brain development and explore current strategies for pinpointing these differences.

scholarly journals Modeling PTEN overexpression-induced microcephaly in human brain organoids

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Navroop Dhaliwal ◽  
Wendy W.Y. Choi ◽  
Julien Muffat ◽  
Yun Li
Keyword(s):  
Human Brain ◽  
Human Genetics ◽  
Negative Regulator ◽  
Akt Inhibitor ◽  
Chromosome 10 ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Pi3k Signaling Pathway ◽  
Brain Organoid ◽  
Phosphoinositide 3 Kinase

AbstractThe phosphatase and tensin homolog (PTEN) protein, encoded by the PTEN gene on chromosome 10, is a negative regulator of the phosphoinositide 3-kinase (PI3K) signaling pathway. Loss of PTEN has been linked to an array of human diseases, including neurodevelopmental disorders such as macrocephaly and autism. However, it remains unknown whether increased dosage of PTEN can lead to human disease. A recent human genetics study identifies chromosome 10 microduplication encompassing PTEN in patients with microcephaly. Here we generated a human brain organoid model of increased PTEN dosage. We showed that mild PTEN overexpression led to reduced neural precursor proliferation, premature neuronal differentiation, and the formation of significantly smaller brain organoids. PTEN overexpression resulted in decreased AKT activation, and treatment of wild-type organoids with an AKT inhibitor recapitulated the reduced brain organoid growth phenotypes. Together, our findings provide functional evidence that PTEN is a dosage-sensitive gene that regulates human neurodevelopment, and that increased PTEN dosage in brain organoids results in microcephaly-like phenotypes.

scholarly journals Modeling HIV-1 neuropathogenesis using three-dimensional human brain organoids (hBORGs) with HIV-1 infected microglia

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Roberta S. dos Reis ◽  
Shilpa Sant ◽  
Hannah Keeney ◽  
Marc C. E. Wagner ◽  
Velpandi Ayyavoo
Keyword(s):  
Human Brain ◽  
Interleukin 1 ◽  
Three Dimensional ◽  
Cell Types ◽  
Great Promise ◽  
Experimental Systems ◽  
Molecular Events ◽  
Hiv Neuropathogenesis ◽  
Brain Organoid ◽  
Hiv 1

Abstract HIV-1 associated neurocognitive disorder (HAND) is characterized by neuroinflammation and glial activation that, together with the release of viral proteins, trigger a pathogenic cascade resulting in synaptodendritic damage and neurodegeneration that lead to cognitive impairment. However, the molecular events underlying HIV neuropathogenesis remain elusive, mainly due to lack of brain-representative experimental systems to study HIV-CNS pathology. To fill this gap, we developed a three-dimensional (3D) human brain organoid (hBORG) model containing major cell types important for HIV-1 neuropathogenesis; neurons and astrocytes along with incorporation of HIV-infected microglia. Both infected and uninfected microglia infiltrated into hBORGs resulting in a triculture system (MG-hBORG) that mirrors the multicellular network observed in HIV-infected human brain. Moreover, the MG-hBORG model supported productive viral infection and exhibited increased inflammatory response by HIV-infected MG-hBORGs, releasing tumor necrosis factor (TNF-α) and interleukin-1 (IL-1β) and thereby mimicking the chronic neuroinflammatory environment observed in HIV-infected individuals. This model offers great promise for basic understanding of how HIV-1 infection alters the CNS compartment and induces pathological changes, paving the way for discovery of biomarkers and new therapeutic targets.

Moral Status of Brain Organoids

2021 ◽  
pp. 250-268
Author(s):  
Julian Koplin ◽  
Olivia Carter ◽  
Julian Savulescu
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Stem Cell Research ◽  
Cognitive Abilities ◽  
Moral Status ◽  
Ethical Challenges ◽  
Moral Framework ◽  
Brain Organoid ◽  
Regulations And Guidelines

Brain organoid research raises ethical challenges not seen in other forms of stem cell research. Given that brain organoids recapitulate the development of the human brain, it is plausible that brain organoids could one day attain consciousness and perhaps even higher cognitive abilities. Brain organoid research therefore raises difficult questions about these organoids’ moral status—questions that currently fall outside the scope of existing regulations and guidelines. This chapter offers a novel moral framework for brain organoid research. It outlines the conditions under which brain organoids might attain moral status and explain what this means for the ethics of experimenting with these entities.

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