scholarly journals In Vitro Recapitulation of Neuropsychiatric Disorders with Pluripotent Stem Cells-Derived Brain Organoids

2021 ◽  
Vol 18 (23) ◽  
pp. 12431
Author(s):  
Maisumu Gulimiheranmu ◽  
Shuang Li ◽  
Junmei Zhou
Keyword(s):  
Stem Cells ◽  
Brain Development ◽  
Pluripotent Stem Cells ◽  
Neural Circuit ◽  
Neuropsychiatric Disorders ◽  
Current Application ◽  
Before And After ◽  
Vitro Model ◽  
Abnormal Brain

Adolescent neuropsychiatric disorders have been recently increasing due to genetic and environmental influences. Abnormal brain development before and after birth contribute to the pathology of neuropsychiatric disorders. However, it is difficult to experimentally investigate because of the complexity of brain and ethical constraints. Recently generated human brain organoids from pluripotent stem cells are considered as a promising in vitro model to recapitulate brain development and diseases. To better understand how brain organoids could be applied to investigate neuropsychiatric disorders, we analyzed the key consideration points, including how to generate brain organoids from pluripotent stem cells, the current application of brain organoids in recapitulating neuropsychiatric disorders and the future perspectives. This review covered what have been achieved on modeling the cellular and neural circuit deficits of neuropsychiatric disorders and those challenges yet to be solved. Together, this review aims to provide a fundamental understanding of how to generate brain organoids to model neuropsychiatric disorders, which will be helpful in improving the mental health of adolescents.

scholarly journals An in vitro model of human neocortical development using pluripotent stem cells: cocaine-induced cytoarchitectural alterations

2014 ◽  
Vol 7 (12) ◽  
pp. 1397-1405 ◽  
Author(s):  
A. A. Kindberg ◽  
R. M. Bendriem ◽  
C. E. Spivak ◽  
J. Chen ◽  
A. Handreck ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
In Vitro Model ◽  
Neocortical Development ◽  
Vitro Model

scholarly journals Testing the Stability of Drug Resistance on Cryopreserved, Gene-Engineered Human Induced Pluripotent Stem Cells

2021 ◽  
Vol 14 (9) ◽  
pp. 919
Author(s):  
Dilaware Khan ◽  
Ann-Christin Nickel ◽  
Sebastian Jeising ◽  
Constanze Uhlmann ◽  
Sajjad Muhammad ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Development ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Medium Size ◽  
Long Term Storage ◽  
Before And After ◽  
In Vitro Pharmacology ◽  
Induced Pluripotent

Human induced pluripotent stem cells (hiPSCs) have emerged as a powerful tool for in vitro modelling of diseases with broad application in drug development or toxicology testing. These assays usually require large quantities of hiPSC, which can entail long-term storage via cryopreservation of the same cell charges. However, it is essential that cryopreservation does not oppose durable changes on the cells. In this project, we characterize one parameter of functionality of one that is well established in the field, in a different research context, an applied hiPSC line (iPS11), namely their resistance to a medium size library of chemo interventions (>160 drugs). We demonstrate that cells, before and after cryopreservation, do not change their relative overall drug response phenotypes, as defined by identification of the top 20 interventions causing dose-dependent reduction of cell growth. Importantly, also frozen cells that are exogenously enforced for stable overexpression of oncogenes myelocytomatosis (cMYC) or tumor protein 53 mutation (TP53R175H), respectively, are not changed in their relative top 20 drugs response compared to their non-frozen counterparts. Taken together, our results support iPSCs as a reliable in vitro platform for in vitro pharmacology, further raising hopes that this technology supports biomarker-associated drug development. Given the general debate on ethical and economic problems associated with the reproducibly crisis in biomedicine, our results may be of interest to a wider audience beyond stem cell research.

scholarly journals Pluripotent Stem Cells as an In Vitro Model of Neuronal Differentiation

10.5772/24695 ◽  
2011 ◽  
Author(s):  
Irina Kerkis ◽  
Mirian A. F. Hayashi ◽  
Nelson F. ◽  
Antonio C. ◽  
Lygia V. ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neuronal Differentiation ◽  
Pluripotent Stem Cells ◽  
In Vitro Model ◽  
Vitro Model

scholarly journals Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness

2015 ◽  
Vol 112 (41) ◽  
pp. 12705-12710 ◽  
Author(s):  
Alexandre J. S. Ribeiro ◽  
Yen-Sin Ang ◽  
Ji-Dong Fu ◽  
Renee N. Rivas ◽  
Tamer M. A. Mohamed ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Contractile Activity ◽  
Cellular Level ◽  
Substrate Stiffness ◽  
Tubule Formation ◽  
Aspect Ratios ◽  
Mitochondrial Distribution ◽  
Vitro Model

Single cardiomyocytes contain myofibrils that harbor the sarcomere-based contractile machinery of the myocardium. Cardiomyocytes differentiated from human pluripotent stem cells (hPSC-CMs) have potential as an in vitro model of heart activity. However, their fetal-like misalignment of myofibrils limits their usefulness for modeling contractile activity. We analyzed the effects of cell shape and substrate stiffness on the shortening and movement of labeled sarcomeres and the translation of sarcomere activity to mechanical output (contractility) in live engineered hPSC-CMs. Single hPSC-CMs were cultured on polyacrylamide substrates of physiological stiffness (10 kPa), and Matrigel micropatterns were used to generate physiological shapes (2,000-µm2 rectangles with length:width aspect ratios of 5:1–7:1) and a mature alignment of myofibrils. Translation of sarcomere shortening to mechanical output was highest in 7:1 hPSC-CMs. Increased substrate stiffness and applied overstretch induced myofibril defects in 7:1 hPSC-CMs and decreased mechanical output. Inhibitors of nonmuscle myosin activity repressed the assembly of myofibrils, showing that subcellular tension drives the improved contractile activity in these engineered hPSC-CMs. Other factors associated with improved contractility were axially directed calcium flow, systematic mitochondrial distribution, more mature electrophysiology, and evidence of transverse-tubule formation. These findings support the potential of these engineered hPSC-CMs as powerful models for studying myocardial contractility at the cellular level.

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