Human pluripotent stem cell-based approaches for myocardial repair: from the electrophysiological perspective.

Mol Pharm

Stem Cell & Regenerative Medicine Consortium, LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong.

Published: October 2011

Heart diseases are a leading cause of mortality worldwide. Terminally differentiated adult cardiomyocytes (CMs) lack the innate ability to regenerate. Their malfunction or significant loss can lead to conditions from cardiac arrhythmias to heart failure. For myocardial repair, cell- and gene-based therapies offer promising alternatives to donor organ transplantation. Human embryonic stem cells (hESCs) can self-renew while maintaining their pluripotency. Direct reprogramming of adult somatic cells to become pluripotent hES-like cells (also known as induced pluripotent stem cells or iPSCs) has been achieved. Both hESCs and iPSCs have been successfully differentiated into genuine human CMs. In this review, we describe our current knowledge of the structure-function properties of hESC/iPSC-CMs, with an emphasis on their electrophysiology and Ca(2+) handling, along with the hurdles faced and potential solutions for translating into clinical and other applications (e.g., disease modeling, cardiotoxicity and drug screening).

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362797PMC
http://dx.doi.org/10.1021/mp2002363DOI Listing

Publication Analysis

Top Keywords

pluripotent stem
8
myocardial repair
8
stem cells
8
human pluripotent
4
stem cell-based
4
cell-based approaches
4
approaches myocardial
4
repair electrophysiological
4
electrophysiological perspective
4
perspective heart
4

Similar Publications

Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs.

View Article and Find Full Text PDF

Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), nearly 20% of hospitalized patients are at risk for thromboembolic events. This prothrombotic state is considered a key factor in the increased risk of stroke, which is observed clinically during both acute infection and long after symptoms clear. Here, we develop a model of SARS-CoV-2 infection using human-induced pluripotent stem cell-derived endothelial cells (ECs), pericytes (PCs), and smooth muscle cells (SMCs) to recapitulate the vascular pathology associated with SARS-CoV-2 exposure.

View Article and Find Full Text PDF

Robust and inducible genome editing via an all-in-one prime editor in human pluripotent stem cells.

Nat Commun

December 2024

The SKI Stem Cell Research Facility, The Center for Stem Cell Biology and Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY, USA.

Prime editing (PE) allows for precise genome editing in human pluripotent stem cells (hPSCs), such as introducing single nucleotide modifications, small insertions or deletions at a specific genomic locus. Here, we systematically compare a panel of prime editing conditions in hPSCs and generate a potent prime editor, "PE-Plus", through co-inhibition of mismatch repair and p53-mediated cellular stress responses. We further establish an inducible prime editing platform in hPSCs by incorporating the PE-Plus into a safe-harbor locus and demonstrated temporal control of precise editing in both hPSCs and differentiated cells.

View Article and Find Full Text PDF

Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discover that hippocampal and spinal cord motor neurons of mouse and human origin localize a subset of chaperone mRNAs to their dendrites and use microtubule-based transport to increase this asymmetric localization following proteotoxic stress.

View Article and Find Full Text PDF

DLK-dependent axonal mitochondrial fission drives degeneration after axotomy.

Nat Commun

December 2024

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!