Cerebral organoids model human brain development and microcephaly
Madeline A. Lancaster,Magdalena Renner,Carol Anne Martin,Daniel Wenzel,Louise S. Bicknell,Matthew E. Hurles,Tessa Homfray,Josef M. Penninger,Andrew P. Jackson,Juergen A. Knoblich +9 more
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TLDR
A human pluripotent stem cell-derived three-dimensional organoid culture system that develops various discrete, although interdependent, brain regions that include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes is developed.Abstract:
The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissueread more
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hiPSC-derived iMSCs: NextGen MSCs as an advanced therapeutically active cell resource for regenerative medicine
Vikram Sabapathy,Sanjay Kumar +1 more
TL;DR: The role of iPSC‐derived mesenchymal stromal cells (iMSCs) as an alternate source of therapeutically active MSCs is described and the necessary strategies and regulatory policies that have to be enforced to render iMSC's effectiveness in translational medicine are described.
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Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip
Stephanie Dauth,Ben M. Maoz,Sean P. Sheehy,Matthew A. Hemphill,Tara Murty,Mary Kate Macedonia,Angie M. Greer,Bogdan Budnik,Kevin Kit Parker +8 more
TL;DR: A novel brain-on-a-chip model is introduced that enables the development of unique disease models incorporating essential in vivo features, such as different brain areas and their functional connections and introduces a novel multiregional brain in vitro models.
Journal ArticleDOI
Cerebral organoid and mouse models reveal a RAB39b–PI3K–mTOR pathway-dependent dysregulation of cortical development leading to macrocephaly/autism phenotypes
Wei Zhang,Li Ma,Mei Yang,Qiang Shao,Jian Xu,Zhipeng Lu,Zhen Zhao,Rong Chen,Yang Chai,Jian-Fu Chen +9 more
TL;DR: Mechanistic studies reveal that RAB39b mutation promotes PI3K-AKT-mTOR activity and alters cortical neurogenesis, leading to macrocephaly and autistic-like behaviors, and provides new insights into neurodevelopmental dysregulation and common pathways associated with ASD across species.
Journal ArticleDOI
Vascularized microfluidic organ-chips for drug screening, disease models and tissue engineering
TL;DR: In this article, the authors describe the latest developments in vascularization and prevascularization of micro-tissues and provide an outlook on potential future strategies, including 3D bioprinting and in vitro angiogenesis and vasculogenesis could be applied to vascularize a range of tissues and organoids.
Journal ArticleDOI
A LUHMES 3D dopaminergic neuronal model for neurotoxicity testing allowing long-term exposure and cellular resilience analysis
Lena Smirnova,Georgina Harris,Johannes Delp,Marize Campos Valadares,David Pamies,Helena T. Hogberg,Tanja Waldmann,Marcel Leist,Thomas Hartung,Thomas Hartung +9 more
TL;DR: Down-regulation of mir-7, a miRNA known to target alpha-synuclein and to be involved in PD, is shown for the first time in LUHMES, and the model appears to be suitable to address the processes of resilience and recovery in neurotoxicology and Parkinson’s disease in future studies.
References
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