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Non-invasive maturity assessment of iPSC-CMs based on optical maturity characteristics using interpretable AI
Scheurer, Fabian, Hammer, Alexander, Schubert, Mario, Steiner, Robert-Patrick, Gamm, Oliver, Guan, Kaomei, Sonntag, Frank, Malberg, Hagen, Schmidt, Martin
Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are an important resource for the identification of new therapeutic targets and cardioprotective drugs. After differentiation iPSC-CMs show an immature, fetal-like phenotype. Cultivation of iPSC-CMs in lipid-supplemented maturation medium (MM) strongly enhances their structural, metabolic and functional phenotype. Nevertheless, assessing iPSC-CM maturation state remains challenging as most methods are time consuming and go in line with cell damage or loss of the sample. To address this issue, we developed a non-invasive approach for automated classification of iPSC-CM maturity through interpretable artificial intelligence (AI)-based analysis of beat characteristics derived from video-based motion analysis. In a prospective study, we evaluated 230 video recordings of early-state, immature iPSC-CMs on day 21 after differentiation (d21) and more mature iPSC-CMs cultured in MM (d42, MM). For each recording, 10 features were extracted using Maia motion analysis software and entered into a support vector machine (SVM). The hyperparameters of the SVM were optimized in a grid search on 80 % of the data using 5-fold cross-validation. The optimized model achieved an accuracy of 99.5 $\pm$ 1.1 % on a hold-out test set. Shapley Additive Explanations (SHAP) identified displacement, relaxation-rise time and beating duration as the most relevant features for assessing maturity level. Our results suggest the use of non-invasive, optical motion analysis combined with AI-based methods as a tool to assess iPSC-CMs maturity and could be applied before performing functional readouts or drug testing. This may potentially reduce the variability and improve the reproducibility of experimental studies.
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- Research Report > New Finding (1.00)
- Research Report > Experimental Study (1.00)
Scientists may be soon be able to grow replicas of human brains in a lab
Scientists may soon be able to create human brains in a lab, according to the latest research. For the first time scientists have successfully grown a 3D model of the brain using human cells, allowing them to better study abnormal brain activity. Experts have been culturing brain tissue for years but this technique uses functional neutral tissue to create'brain-like organoids'. Researchers say in the future they could use cells from patients with Parkinson's and Alzheimer's to understand how they will respond to certain treatments. Scientists have successfully grown a 3D model of the brain from human neurons, providing them with a better opportunity to study abnormal brain cells.
Scientists may now be able to grow a brain using human neurons
Scientists may have made a major leap forward on the path to growing a fully-formed human brain in the lab. According to a new study, researchers at Tufts University have now grown a 3D tissue model of the brain using human neurons, providing them with a better opportunity to study abnormal brain cells. Though brain tissue cells have been cultured for years under laboratory conditions, this technique employs a three-dimensional scaffold of functional neural tissue. The researchers used human induced pluripotent stem cells or iPSCs taken from a variety of sources to create "brain-like organoids." "We found the right conditions to get the iPSCs to differentiate into a number of different neural subtypes, as well as astrocytes that support the growing neural networks," said David Kaplan from Tufts.
- Health & Medicine > Therapeutic Area > Neurology (1.00)
- Health & Medicine > Therapeutic Area > Hematology > Stem Cells (0.60)
Scientists grow functioning human neural networks in 3-D from stem cells
A team of Tufts University-led researchers has developed three-dimensional (3-D) human tissue culture models for the central nervous system that mimic structural and functional features of the brain and demonstrate neural activity sustained over a period of many months. With the ability to populate a 3-D matrix of silk protein and collagen with cells from patients with Alzheimer's disease, Parkinson's disease, and other conditions, the tissue models allow for the exploration of cell interactions, disease progression and response to treatment. The development and characterization of the models are reported today in ACS Biomaterials Science & Engineering, a journal of the American Chemical Society. The new 3-D brain tissue models overcome a key challenge of previous models -the availability of human source neurons. This is due to the fact that neurological tissues are rarely removed from healthy patients and are usually only available post-mortem from diseased patients.