sarcomere-shortening-pluripotent-stem-cell-derived-cardiomyocytes

Sarcomere Shortening of Pluripotent Stem Cell-Derived Cardiomyocytes using Fluorescent-Tagged Sarcomere Proteins.

Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) can be produced from both embryonic and induced pluripotent stem (ES/iPS) cells. These cells ...

Jichi Medical University

Intravenous immunoglobulin therapy is standard for Kawasaki disease (KD) treatment; however, anaphylactic reactions to immunoglobulins are a risk in KD patients with selective IgA deficiency (sIgAD). The therapy for KD associated with sIgAD has not been established. The IgA immune response is believed to play an important role in KD vasculitis. We report the case of a 5-year-old boy with KD and sIgAD treated with intravenous cyclosporine A (CsA, 3.0 mg/kg/day) instead of intravenous immunoglobulin (IVIG). The fever and inflammation immediately resolved without a coronary artery lesion. In KD patients with sIgAD, we believe that an IgA immune response is lacking, which is the reason for milder KD symptoms than in those without sIgAD. This case report aids in clarifying the role of IgA antibodies in KD and provides evidence that CsA is a potential candidate for first-line therapy for patients with KD with contraindications to IVIG.

Treatment of a patient with Kawasaki disease associated with selective IgA deficiency by continuous infusion of cyclosporine A without intravenous immunoglobulin.

Cardiovascular diseases are the leading cause of death worldwide. Therefore, the discovery of induced pluripotent stem cells (iPSCs) and the subsequent generation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) was a pivotal point in regenerative medicine and cardiovascular research. They constituted an appealing tool for replacing dead and dysfunctional cardiac tissue, screening cardiac drugs and toxins, and studying inherited cardiac diseases. The problem is that these cells remain largely immature, and in order to utilize them, they must reach a functional degree of maturity. To attempt to mimic  environment, various methods including prolonging culture time, co-culture and modulations of chemical, electrical, mechanical culture conditions have been tried. In addition to that, changing the topology of the culture made huge progress with the introduction of the 3D culture that closely resembles the  cardiac topology and overcomes many of the limitations of the conventionally used 2D models. Nonetheless, 3D culture alone is not enough, and using a combination of these methods is being explored. In this review, we summarize the main differences between immature, fetal-like hiPSC-CMs and adult cardiomyocytes, then glance at the current approaches used to promote hiPSC-CMs maturation. In the second part, we focus on the evolving 3D culture model - it's structure, the effect on hiPSC-CMs maturation, incorporation with different maturation methods, limitations and future prospects.

A Brief Review of Current Maturation Methods for Human Induced Pluripotent Stem Cells-Derived Cardiomyocytes.

Transcriptome landscape of organs from mice and humans offers perspectives on the process of how organs develop and the similarity and diversity in each organ between the species. Among multi-species and multi-organ dataset, which was previously generated, we focused on the mouse and human dataset and performed a reanalysis to provide a more specific perspective on the maturation of human cardiomyocytes. First, we examined how organs diversify their transcriptome during development across and within two species. We unexpectedly identified that ribosomal genes were differentially expressed between mice and humans. Second, we examined the corresponding ages of organs in mice and humans and found that the corresponding developmental ages did not match throughout organs. Mouse hearts at P0-3 and human hearts at 18-19 wpc showed the most proximity in the regard of the transcriptome. Third, we identified a novel set of maturation marker genes that are more consistent between mice and humans. In contrast, conventionally used maturation marker genes only work well with mouse hearts. Finally, we compared human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) in maturation-enhanced conditions to human fetal and adult hearts and revealed that human PSC-CMs only expressed low levels of the potential maturation marker genes. Our findings provide a novel foundation to study cardiomyocyte maturation and highlight the importance of studying human samples rather than relying on a mouse time-series dataset.

Comparative Transcriptome Landscape of Mouse and Human Hearts.

Although genetic factors are involved in the etiology of autism spectrum disorder (ASD), the significance of genetic analysis in clinical settings is unclear. Forty-nine subjects diagnosed with non-syndromic ASD were analyzed by microarray comparative genomic hybridization (CGH) analysis, whole-exome sequencing (WES) analysis, and panel sequencing analysis for 52 common causative genes of ASD to detect inherited rare variants. Genetic analysis by microarray CGH and WES analyses showed conclusive results in about 10% of patients, however, many inherited variants detected by panel sequencing analysis were difficult to interpret and apply in clinical practice in the majority of patients. Further improvement of interpretation of many variants detected would be necessary for combined genetic tests to be used in clinical settings.

Article	Year
Treatment of a patient with Kawasaki disease associated with selective IgA deficiency by continuous infusion of cyclosporine A without intravenous immunoglobulin. The Turkish journal of pediatrics\| PubMed ID: 29090883	2016
A Brief Review of Current Maturation Methods for Human Induced Pluripotent Stem Cells-Derived Cardiomyocytes. Frontiers in cell and developmental biology\| PubMed ID: 32266260	2020
Comparative Transcriptome Landscape of Mouse and Human Hearts. Frontiers in cell and developmental biology\| PubMed ID: 32391358	2020
Comprehensive Genetic Analysis of Non-syndromic Autism Spectrum Disorder in Clinical Settings. Journal of autism and developmental disorders\| PubMed ID: 33590427	2021

Tatsuya Anzai

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