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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Structural Immaturity of Human iPSC-Derived Cardiomyocytes: In Silico Investigation of Effects on Function and Disease Modeling
|
|---|---|
| Published in |
Frontiers in Physiology, February 2018
|
| DOI | 10.3389/fphys.2018.00080 |
| Pubmed ID | |
| Authors |
Jussi T. Koivumäki, Nikolay Naumenko, Tomi Tuomainen, Jouni Takalo, Minna Oksanen, Katja A. Puttonen, Šárka Lehtonen, Johanna Kuusisto, Markku Laakso, Jari Koistinaho, Pasi Tavi |
| Abstract |
Background: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising experimental tool for translational heart research and drug development. However, their usability as a human adult cardiomyocyte model is limited by their functional immaturity. Our aim is to analyse quantitatively those characteristics and how they differ from adult CMs.Methods and Results:We have developed a novelin silicomodel with all essential functional electrophysiology and calcium handling features of hiPSC-CMs. Importantly, the virtual cell recapitulates the immature intracellular ion dynamics that are characteristic for hiPSC-CMs, as quantified based ourin vitroimaging data. The strong "calcium clock" is a source for a dual function of excitation-contraction coupling in hiPSC-CMs: action potential and calcium transient morphology vary substantially depending on the activation sequence of underlying ionic currents and fluxes that is altered in spontaneous vs. paced mode. Furthermore, parallel simulations with hiPSC-CM and adult cardiomyocyte models demonstrate the central differences. Results indicate that hiPSC-CMs translate poorly the disease specific phenotypes of Brugada syndrome, long QT Syndrome and catecholaminergic polymorphic ventricular tachycardia, showing less robustness and greater tendency for arrhythmic events than adult CMs. Based on a comparative sensitivity analysis, hiPSC-CMs share some features with adult CMs, but are still functionally closer to prenatal CMs than adult CMs. A database analysis of 3000 hiPSC-CM model variants suggests that hiPSC-CMs recapitulate poorly fundamental physiological properties of adult CMs. Single modifications do not appear to solve this problem, which is mostly contributed by the immaturity of intracellular calcium handling.Conclusion:Our data indicates that translation of findings from hiPSC-CMs to human disease should be made with great caution. Furthermore, we established a mathematical platform that can be used to improve the translation from hiPSC-CMs to human, and to quantitatively evaluate hiPSC-CMs development toward more general and valuable model for human cardiac diseases. |
X Demographics
The data shown below were collected from the profiles of 22 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Switzerland | 2 | 9% |
| Indonesia | 1 | 5% |
| Chile | 1 | 5% |
| Saudi Arabia | 1 | 5% |
| Greece | 1 | 5% |
| South Africa | 1 | 5% |
| Brazil | 1 | 5% |
| Colombia | 1 | 5% |
| Finland | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 11 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 19 | 86% |
| Practitioners (doctors, other healthcare professionals) | 2 | 9% |
| Scientists | 1 | 5% |
Mendeley readers
The data shown below were compiled from readership statistics for 223 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 223 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 51 | 23% |
| Researcher | 38 | 17% |
| Student > Master | 27 | 12% |
| Student > Bachelor | 25 | 11% |
| Student > Doctoral Student | 13 | 6% |
| Other | 23 | 10% |
| Unknown | 46 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 51 | 23% |
| Medicine and Dentistry | 23 | 10% |
| Engineering | 21 | 9% |
| Agricultural and Biological Sciences | 20 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 16 | 7% |
| Other | 32 | 14% |
| Unknown | 60 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 12. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 December 2020.
All research outputs
#2,928,843
of 25,137,221 outputs
Outputs from Frontiers in Physiology
#1,553
of 15,450 outputs
Outputs of similar age
#64,258
of 449,303 outputs
Outputs of similar age from Frontiers in Physiology
#45
of 302 outputs
Altmetric has tracked 25,137,221 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 15,450 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.0. This one has done well, scoring higher than 89% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 449,303 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 302 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 85% of its contemporaries.