The structural and functional maturation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is essential for pharmaceutical testing, disease modeling, and ultimately therapeutic use. Multicellular 3D-tissue platforms have improved the functional maturation of hiPSC-CMs, but probing cardiac contractile properties in a 3D environment remains challenging, especially at depth and in live tissues. Using small-angle X-ray scattering (SAXS) imaging, we show that hiPSC-CMs matured and examined in a 3D environment exhibit a periodic spatial arrangement of the myofilament lattice, which has not been previously detected in hiPSC-CMs. The contractile force is found to correlate with both the scattering intensity (  = 0.44) and lattice spacing (  = 0.46). The scattering intensity also correlates with lattice spacing (  = 0.81), suggestive of lower noise in our structural measurement than in the functional measurement. Notably, we observed decreased myofilament ordering in tissues with a myofilament mutation known to lead to hypertrophic cardiomyopathy (HCM). Our results highlight the progress of human cardiac tissue engineering and enable unprecedented study of structural maturation in hiPSC-CMs.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433147PMC
http://dx.doi.org/10.1038/s41378-020-00234-xDOI Listing

Publication Analysis

Top Keywords

functional maturation
8
maturation hipsc-cms
8
scattering intensity
8
lattice spacing
8
hipsc-cms
5
probing subcellular
4
subcellular nanostructure
4
nanostructure engineered
4
engineered human
4
human cardiomyocytes
4

Similar Publications

Background: Obtaining information about the growth rates of animals' organs and tissues can help understand their meat production potential and determine the ideal slaughter weight (SW).

Objectives: This study aimed to determine the effects of production system and SW on the allometric growth of the non-carcass components, carcass cuts, and hind limb tissues of Kivircik lambs.

Methods: A total of 54 single-born male lambs were randomly allocated into production systems (concentrate- and pasture-based) and SW groups: 25-26 kg (LOW), 30-31 kg (MEDIUM), and 35-36 kg (HIGH).

View Article and Find Full Text PDF

Tumor-promoting inflammation significantly impacts cancer progression, and targeting inflammatory cytokines has emerged as a promising therapeutic approach in clinical trials. Interleukin (IL)-1α, a member of the IL-1 cytokine family, plays a crucial role in both inflammation and carcinogenesis. How IL-1α is secreted in the tumor microenvironment has been poorly understood, and we previously showed that calpain 1 cleaves pro-IL-1α for mature IL-1α secretion, which exacerbates hepatocellular carcinoma by recruiting myeloid-derived suppressor cells.

View Article and Find Full Text PDF

Aim: Despite dysfunctional vasoactive intestinal polypeptide-positive interneurons (VIP-INs) being linked to the emergence of neurodevelopmental disorders, the temporal profile of VIP-IN functional maturation and cortical network integration remains unclear.

Methods: Postnatal VIP-IN development was traced with patch clamp experiments in the somatosensory cortex of Vip-IRES-cre x tdTomato mice. Age groups were chosen during barrel field formation, before and after activation of main sensory inputs, and in adult animals (postnatal days (P) P3-4, P8-10, P14-16, and P30-36).

View Article and Find Full Text PDF

Cardiac growth patterns and metabolism before and after birth in swine: Role of miR in proliferation, hypertrophy and metabolism.

J Mol Cell Cardiol Plus

September 2024

Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia.

The adult mammalian heart is unable to undergo cardiac repair, limiting potential treatment options after cardiac damage. However, the fetal heart is capable of cardiac repair. In preparation for birth, cardiomyocytes (CMs) undergo major maturational changes that include exit from the cell cycle, hypertrophic growth, and mitochondrial maturation.

View Article and Find Full Text PDF

Expansion of home hemodialysis (HHD) provides an opportunity to improve clinical outcomes, reduce cost of care, and address the staffing challenges currently faced in caring for patients with kidney failure on replacement therapy. To increase HHD expansion, current practices and barriers to home dialysis must be examined and addressed. One such barrier is vascular access for HHD; although tunneled hemodialysis central venous catheters (CVCs) have been used for decades, physicians still hesitate to send patients home without a mature, functional arteriovenous access.

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!